PROPOSED EXPANSION OF BULK DRUGS AND …environmentclearance.nic.in/writereaddata/Online/TOR/22...Construction, operation or decommissioning of the Project involving actions, which

1

FORM-1

for

PROPOSED EXPANSION OF BULK DRUGS AND BULK

DRUG INTERMEDIATES IN EXISTING MANUFACTURING

UNIT

of

M/S. ANMOL ANTIOXIDANTS PVT. LTD.

SURVEY NO. 35 & 36, BEHIND HGI FOUNDARY,

VILL: BASKA-389350, TAL: HALOL,

DIST: PANCHMAHAL ,GUJARAT

NABL Accredited Testing Laboratory

ISO 9001:2008 Certified Company

Aqua-Air Environmental Engineers P. Ltd.

403, Centre Point, Nr. Kadiwala School, Ring

Road, Surat - 395002

Prepared By:











Prepared By:

2

APPENDIX I

(See paragraph - 6)

FORM 1

(I) Basic Information

Sr.

No.

Item Details

1. Name of the project/s M/s. Anmol Antioxidants Pvt. Ltd.

2. S. No. in the schedule 5(f)

3. Proposed capacity/area/length/tonnage to

be handled/command area/lease

area/number of wells to be drilled

For detail Please refer Annexure – I

4. New/Expansion/Modernization Expansion

5. Existing Capacity/Area etc. For detail Please refer Annexure- I

6. Category of Project i.e. ‘A’ or ‘B’ 'A'

7. Does it attract the general condition? If yes,

please specify. No

8. Does it attract the specific condition? If yes,

please specify.

No

9. Location

Plot/Survey/Khasra No. Survey No. 35 & 36, B/h. HGI Foundary

Village Baska-389350

Tehsil Halol

District Panchmahal

State Gujarat

10. Nearest railway station/airport along with

distance in kms.

Nearest Railway Station: Vadodara (40 Km)

Nearest Airport: Vadodara ( 35 km)

11. Nearest Town, city, District Headquarters

along with distance in kms.

Nearest City: Vadodara (40 Km)

District Headquarters :Godhra (46 km)

12. Village Panchayats, Zilla Parishad, Municipal

Corporation, local body (complete postal

address with telephone nos. to be given)

Baska , Taluka: Halol ,Dist: Panchmahal

13. Name of the applicant M/s. Anmol Antioxidants P. Ltd.

14. Registered Address M/s Anmol Antioxidants Pvt. Ltd.

Survey No. 35 & 36, B/h. HGI Foundary, Vill:

Baska-389350,Taluka: Halol, Dist: Panchmahal,

Gujarat

15. Address for correspondence:

Name Mr. Girish D. Vachhani / Mr. Ramesh

Chodvadia

Designation (Owner/Partner/CEO) Director

Address M/s Anmol Antioxidants Pvt. Ltd.

Survey No. 35 & 36, B/h. HGI Foundary, Vill:

Baska-389350,Taluka: Halol, Dist: Panchmahal,

Gujarat

Pin Code 389350

E-mail [email protected]

Telephone No. +919825205460

3

Fax No. --

16. Details of Alternative Sites examined, if any.

Location of these sites should be shown on a

topo sheet.

NA

17. Interlinked Projects No

18. Whether separate application of interlinked

project has been submitted?

No

19. If yes, date of submission No

20. If no, reason No

21. Whether the proposal involves

approval/clearance under: if yes, details of

the same and their status to be given.

(a) The Forest (Conservation) Act, 1980?

(b) The Wildlife (Protection) Act, 1972?

(c) The C.R.Z. Notification, 1991?

No

22. Whether there is any Government

Order/Policy relevant/relating to the site?

No

23. Forest land involved (hectares) No

24. Whether there is any litigation pending

against the project and/or land in which the

project is propose to be set up?

(a) Name of the Court

(b) Case No.

(c) Orders/directions of the Court, if any and

its relevance with the proposed project.

No

Capacity corresponding to sectoral activity (such as production capacity for manufacturing, mining

lease area and production capacity for mineral production, area for mineral exploration, length for

linear transport infrastructure, generation capacity for power generation etc.,)

4

(II) Activity

1. Construction, operation or decommissioning of the Project involving actions, which will cause

physical changes in the locality (topography, land use, changes in water bodies, etc.)

Sr.

No.

Information/Checklist confirmation Yes/

No

Details thereof with approximate

quantities frates, wherever possible) with

source of information data

1.1 Permanent or temporary change in land

use, land cover or topography including

increase intensity of land use (with

respect to local land use plan)

No Proposed Expansion will be carried out

within the existing premises.

1.2 Clearance of existing land, vegetation and

Buildings?

Yes Minor site clearance activities shall be

carried out.

1.3 Creation of new land uses?

No

1.4 Pre-construction investigations e.g. bore

Houses, soil testing?

No

1.5 Construction works?

Yes For detail Please refer Annexure – II

1.6 Demolition works? No --

1.7 Temporary sites used for construction

works or housing of construction

workers?

No

1.8 Above ground buildings, structures or

earthworks including linear structures,

cut and fill or excavations

Yes For detail Please refer Annexure – II

1.9 Underground works mining or tunneling?

No

1.10 Reclamation works?

No

1.11 Dredging?

No

1.12 Off shore structures?

No

1.13

Production and manufacturing processes?

Yes List of products is given as Annexure-I and

Manufacturing process is given as

Annexure –III.

1.14 Facilities for storage of goods or

materials?

Yes Areas for storage of raw materials and

finished products will be available.

1.15 Facilities for treatment or disposal of solid

waste or liquid effluents?

Yes Details of the Liquid Effluent is given as

Annexure – V and Details of solid waste is

given as Annexure –VI.

1.16 Facilities for long term housing of

operational workers?

No

1.17 New road, rail or sea traffic during

Construction or Operation?

No

5

1.18 New road, rail, air waterborne or other

transport infrastructure including new or

altered routes and stations, ports,

airports etc?

No

1.19 Closure or diversion of existing transport

routes or infrastructure leading to

changes in traffic movements?

No

1.20 New or diverted transmission lines or

Pipelines?

No

1.21 Impoundment, damming, culverting,

realignment or other changes to the

hydrology of watercourses or aquifers?

No

1.22 Stream crossings?

No

1.23 Abstraction or transfers of water form

ground or surface waters?

Yes Water Source: Bore well

1.24 Changes in water bodies or the land

surface

Affecting drainage or run-off?

No

1.25 Transport of personnel or materials for

construction, operation or

decommissioning?

Yes By road only.

1.26 Long-term dismantling or

decommissioning or restoration works?

No

1.27 Ongoing activity during decommissioning

which could have an impact on the

environment?

No

1.28 Influx of people to an area either

temporarily or permanently?

No

1.29 Introduction of alien species?

No

1.30 Loss of native species or genetic diversity?

No

1.31 Any other actions? No

6

2. Use of Natural resources for construction or operation of the Project (such as land, water, materials

or energy, especially any resources which are non-renewable or in short supply):

Sr.

No.

Information/checklist confirmation Yes/No Details there of (with approximate

quantities frates, wherever possible) with


2.1 Land especially undeveloped or agricultural

land (ha)

No

2.2 Water (expected source & competing users)

unit: KLD

Yes Water Source: Borewell

Please refer Annexure – IV.

2.3 Minerals (MT) No

2.4 Construction material - stone, aggregates,

and / soil (expected source -MT)

Yes Construction materials, like steel, cement,

crushed stones, sand, rubble, etc. required

for the project shall be procured from the

local market of the region.

2.5 Forests and timber (source - MT) No.

2.6 Energy including electricity and fuels

(source, competing users) Unit: fuel (MT),

energy (MW)

Yes Power required : 1500 KW (Proposed)

Source: MGVCL

D.G. Set : 250 KVA

Fuel Requirement:

Existing:

LDO/Wood: 101 KL/Year OR 0.28 MT/Day

Proposed:

Agrowaste Briquette/Bio-coal: 10 MT/Day

LDO: 5 KL/Day

Diesel: 30 Lit/Day

2.7 Any other natural resources (use

appropriate standard units)

No

3. Use, storage, transport, handling or production of substances or materials, which could be

harmful to human health or the environment or raise concerns about actual or perceived risks to

human health.

Sr.

No.

Information/Checklist confirmation Yes/No Details there of (with approximate

quantities/rates, wherever possible) with


3.1 Use of substances or materials, which are

hazardous (as per MSIHC rules) to human

health or the environment (flora, fauna, and

water supplies)

Yes For detail please refer Annexure – VIII.

3.2 Changes in occurrence of disease or affect

disease vectors (e.g. insect or water borne

diseases)

No

3.3 Affect the welfare of people e.g. by changing

living conditions?

No

7

3.4 Vulnerable groups of people who could be

affected by the project e.g. hospital patients,

children, the elderly etc.

No

3.5 Any other causes No

4. Production of solid wastes during construction or operation or decommissioning (MT/month)

Sr.

No.




4.1 Spoil, overburden or mine wastes No

4.2 Municipal waste (domestic and or commercial

wastes)

No

4.3 Hazardous wastes (as per Hazardous Waste

Management Rules)

Yes Please refer Annexure –VI.

4.4 Other industrial process wastes Yes Please refer Annexure- VI.

4.5 Surplus product No

4.6 Sewage sludge or other sludge from effluent

treatment

Yes

Please refer Annexure- VI.

4.7 Construction or demolition wastes No

4.8 Redundant machinery or equipment No

4.9 Contaminated soils or other materials No

4.10 Agricultural wastes No

4.11 Other solid wastes No

5. Release of pollutants or any hazardous, toxic or noxious substances to air (Kg/hr)

Sr.

No.


quantities/rates, wherever possible)

with source of information data

5.1 Emissions from combustion of fossil fuels

from stationary or mobile sources

Yes Please refer as Annexure – VII.

5.2 Emissions from production processes Yes Please refer as Annexure – VII.

5.3 Emissions from materials handling storage or

transport

No

5.4 Emissions from construction activities

including plant and equipment

No

5.5 Dust or odors from handling of materials

including construction materials, sewage and

waste

No

5.6 Emissions from incineration of waste Yes Please refer as Annexure – VII.

5.7 Emissions from burning of waste in open air

(e.g. slash materials, construction debris) No

5.8 Emissions from any other sources No

8

6. Generation of Noise and Vibration, and Emissions of Light and Heat:

Sr.

No.



with source of information data with


6.1 From operation of equipment e.g. engines,

ventilation plant, crushers

Yes The Noise level will be within the

prescribed limit. At noisy area, adequate

preventive & control measures will be

taken. No significant noise, vibration or

emission of light & heat from the unit.

6.2 From industrial or similar processes Yes -do-

6.3 From construction or demolition No

6.4 From blasting or piling No

6.5 From construction or operational traffic No

6.6 From lighting or cooling systems No

6.7 From any other sources No

7. Risks of contamination of land or water from releases of pollutants into the ground or into sewers,

surface waters, groundwater, coastal waters or the sea:

Sr.

No.




7.1 From handling, storage, use or spillage of

hazardous materials

Yes All the raw material shall be stored

separately in designated storage area with

safety measures. For detail please refer

Annexure – VIII

7.2 From discharge of sewage or other effluents

to water or the land (expected mode and

place of discharge)

Yes Sewage shall be disposed of through

specific tank & soak pit system.

7.3 By deposition of pollutants emitted to air into

the and or into water

No

7.4 From any other sources No

7.5 Is there a risk of long term build up of

pollutants in the environment from these

sources?

No

9

8. Risk of accidents during construction or operation of the Project, which could affect human

health or the environment

Sr.

No.




8.1 From explosions, spillages, fires etc. from

storage, handling, use or production of

hazardous substances

Yes For detail please refer Annexure – VIII.

8.2 From any other causes No

8.3 Could the project be affected by natural

disasters causing environmental damage (e.g.

floods, earthquakes, landslides, cloudburst

etc)?

No

9. Factors which should be considered (such as consequential development) which could lead to

environmental effects or the potential for cumulative impacts with other existing or planned

activities in the locality

Sr. No.

Information/Checklist confirmation

Yes/No

Details there of (with approximate



9.1 Lead to development of supporting. lities, ancillary development or development stimulated by the project which could have impact on the environment e.g.

• Supporting infrastructure (roads, power

supply, waste or waste water treatment,

etc.)

• housing development

• extractive industry

• supply industry

• other

Yes For detail please refer Annexure – IX.

9.2 Lead to after-use of the site, which could

have an impact on the environment

No

9.3 Set a precedent for later developments No

9.4 Have cumulative effects due to proximity to

other existing or planned projects with

similar effects

No

10

(II) Environmental Sensitivity

Sr.

No.

Areas Name/

Identity

Aerial distance (within 15km) Proposed

project location boundary

1 Areas protected under international

conventions, national or local legislation for

their ecological, landscape, cultural or other

related value

No

2 Areas which important for are or sensitive

Ecol logical reasons - Wetlands, watercourses

or other water bodies, coastal zone,

biospheres, mountains, forests

No

3 Area used by protected, important or

sensitive Species of flora or fauna for

breeding, nesting, foraging, resting, over

wintering, migration

No

4 Inland, coastal, marine or underground

waters

No

5 State, National boundaries

- N.A.

6 Routes or facilities used by the public for

access to recreation or other tourist, pilgrim

areas

- Public transportation

7 Defense installations - N.A.

8 Densely populated or built-up area Vadodara Vadodara is 40 km from the proposed

expansion project site.

9 Area occupied by sensitive man-made land

uses Hospitals, schools, places of worship,

community facilities)

- N.A.

10 Areas containing important, high quality or

scarce resources (ground water resources,

surface resources, forestry, agriculture,

fisheries, tourism, minerals)

- N.A.

11 Areas already subjected to pollution

environmental damage. (those where existing

legal environmental standards are

exceeded)or

- N.A.

12 Are as susceptible to natural hazard which

could cause the project to present

environmental problems (earthquake s,

subsidence ,landslides, flooding erosion, or

extreme or adverse climatic conditions)

- N.A.

11

12

LIST OF ANNEXURES

SR. NO. NAME OF ANNEXURE

I List of products with their production capacity

II Layout Map of the Plant

III Brief Manufacturing Process Description with Chemical and Mass Balance

IV Details of Water Consumption Wastewater Generation

V Effluent Treatment Scheme

VI Details of Hazardous /Solid Waste Generation, Handling and Disposal

VII Details of Air pollution Control System (Stack & Vent)

VIII Details of Hazardous Chemicals Storage & Handling

IX Socio-economic Impacts

X Proposed Terms of Reference for EIA studies

XI Plot Allotment Letter OR 7/12- COPY

XII CETP Membership Certificate

XIII TSDF Membership Certificate

XIV Toposheet

13

ANNEXURE – 1

LIST OF PRODUCTS WITH THEIR PRODUCTION CAPACITY

LIST OF PRODUCTS

Sr.

No.

NAME OF

PRODUCTS

CAS No. LD50

LC50 Existing

Capacity

MT/Mont

h

Additional

Capacity

MT/Month

Total

Capacity

MT/Month

EXISTING PRODUCTS

1 Ethisterone 434-03-7 300

mg/Kg

-- 0.2 -- 0.2

2 Nandrolone 434-22-0 300

mg/kg

-- 0.1 -- 0.1

3 Betamethasone

valerate

2152-44-5 ORAL

(LD50):

Acute:

4067

mg/kg

[Rat].

-- 0.05 -- 0.05

4 Budesonide 51333-22-3 ORAL

(LD50):

Acute:

3200

mg/kg

[Rat].

4750

mg/kg

[Mouse]

-- 0.03 -- 0.03

5 Mometasone

Furoate

83919-23-7 2000

mg/kg

-- 0.03 -- 0.03

6 Triamcinolone 124-94-7 -- -- 0.03 -- 0.03

7 Betamethasone

Dipropionate

5593-20-4 -- -- 0.05 -- 0.05

8 Clobetasol

propionate

25122-46-7 ORAL

(LD50):

Acute:

>3000

mg/kg

[Rat].

>3000

mg/kg

[Mouse]

-- 0.07 -- 0.07

9 Triamainolone

Acetonide

76-25-5 3000

mg/kg

NA 0.07 -- 0.07

10 Sulphonated

Melamine

9003-08-1 270

mg/kg

203

mg/

16 -- 16

14

Formaldehyde

condensate

Solution

m3

11 Halobetasole

propionate

66852-54-8 - -- 0.03 -- 0.03

12 Dexamethasone

Sodium

Phosphate

2392-39-4 ORAL

(LD50):

Acute:

1800

mg/kg

[Mouse]

-- 0.05 -- 0.05

13 Clobetasol

Butyrate

25122-57-0 6000

mg/kg

-- 0.03 -- 0.03

14 Beclomethasone

Dipropionate

5534-09-8 ORAL

(LD50):

Acute:

3750

mg/kg

[Rat].

5000

mg/kg

[Mouse]

-- 0.03 -- 0.03

15 Prednisolone

sodium

phosphate

125-02-0 360

mg/kg

NA 0.03 -- 0.03

16 Betamethasone

Sodium

phosphate

151-73-5 ORAL

(LD50):

Acute:

1607

mg/kg

[Mouse]

-- 0.05 -- 0.05

17 N (3-bromo

propyl pthalide)

87-41-2 -- -- 5 -- 5

18 Prednisolone

Acetate

52-21-1 ORAL

(LD50):

Acute:

1680

mg/kg

[Mouse]

-- 0.03 -- 0.03

ADDITIONAL PRODUCTS

GROUP- A

19 Acebrofylline 96989-76-3 -- -- - 30 30

20 Ambroxol

Hydrchloride

15942-05-9 2720

mg/kg

--

21 Amlodipine

Besylate

111470-99-6 ORAL

(LD50):

Acute:

--

15

393

mg/kg

[Rat]. 37

mg/kg

[Mouse]

22 Bupropion

Hydrochloride

31677-93-7 ORAL

(LD50):

482

mg/kg

[Rat]. 544

mg/kg

[Mouse]

--

23 Celecoxib 169590-42-5 5

mg/kg

--

24 Doxofylline 69975-86-6 300

mg/kg

--

25 Drotaverine

Hydrochloride

985-12-6 Oral

LD50

(rat): 540

mg/kg;

Oral

LD50

(mouse):

350

mg/kg

--

GROUP- B

26 Etoricoxib 202409-33-4 0.7

mg/kg

-- - 30 30

27 Flurbiprofen 5104-49-4 ORAL

(LD50):

Acute:

117

mg/kg

[Rat]. 640

mg/kg

[Mouse]:

290

mg/kg

[Rabbit].

--

28 Glibenclamide 10238-21-8 LD50

Oral – rat

–>20,000

mg/kg

--

29 Phenazopyridine

Hydrochloride

136-40-3 ORAL

(LD50):

Acute:

472

-

16

mg/kg

[Rat].

30 Phenyl Ephrine 61-76-7 120

mg/kg

--

31 Quetiapine

fumarate

111974-72-2 3.53

µg/kg

--

32 Telmisartan 144701-48-4 3

mg/kg

--

33 Valsartan 137862-53-4 300

mg/kg

--

GROUP- C

34 Bisoprolol

Fumarate

66722-44-9 300

mg/kg

-- - 10 10

35 Brimonidine

Tartrate

70359-46-5 50

mg/kg

--

36 Capacitabine 154361-50-9 2000

mg/kg

--

37 Cinacalcet

Hydrochloride

364782-34-3 300

mg/kg

--

38 Donepezil

Hydrochloride

120011-70-3 32.6

mg/kg

2000

mg/

m3

39 Gemcitabine

Hydrochloride

122111-03-9 333

mg/kg

--

40 Glimepiride 93479-97-1 10000

mg/kg

--

41 Ivabridine 148849-67-6 -- --

42 Nevivolol

Hydrochloride

152520-56-4 300

mg/kg

--

43 Pirfenidone 53179-13-8 Oral

LD50

(rat):

1295

mg/kg;

Oral

LD50

(mouse):

580

mg/kg

--

44 Sofosbuvir 1190307-88-

0

300

mg/kg

--

45 Terbinafine

Hydrochloride

78628-80-5 DERMAL

(LD50):

Acute:

>20000

mg/kg

[Rat].

--

17

46 Ursodeoxycholic

acid

128-13-2 Acute

oral

toxicity

(LD50):

4600

mg/kg

[Rat].

--

GROUP- D

47 2 Amino Phenyl

phenyl Sulfide

1134-94-7 -- -- -- 40 40

48 2 Amino 3,5 Di

bromo

benzaldehyde

50910-55-9 -- --

49 Dibenzo[b,f][1,4]T

hiazepin-11(10H)-

One

3159-07-7 -- --

50 4 Methyl

Acetophenone

122-00-9 LD50

Oral –

rat -

1,400

mg/kg

--

51 2-Chloro-1,3 bis

(dimentylamino)

trimethinium

hexafluoro

phosphate

291756-76-8 -- --

52 2,3-Dibenzoyl-D-

Tartaric acid

17026-42-5 -- --

53 Ethyl Trifluoro

Acetate

383-63-1 -- 7790

-

1280

0

mg/L

54 m Phenoxy benzyl

alcohol

13826-35-2 2040

mg/kg

--

55 p Methoxy Phenyl

Acetonirile

104-47-2 100-125

mg/kg

--

56 Phthaloyl

Amlodipine

88150-62-3 300

mg/kg

--

57 Sulfanilamide 63-74-1 ORAL

(LD50):

Acute:

3900

mg/kg

[Rat].

3000

mg/kg

VAP

OR

(LC5

0):

Acut

e:

255

ppm

18

[Mouse]. 4

hour

(s)

[Rat]

58 3-Trifluoromethyl

Cinnamic Acid

779-89-5 -- --

GROUP- E

59 Glipizide 29094-61-9 5000

mg/kg

-- - 10 10

60 Modafinil 68693-11-8 64

mg/kg

--

61 Mycophenolate

Mofetil

128794-94-5 200

mg/kg

--

62 Tadalafil 171596-29-5 0.29

mg/kg

--

63 Tranexamic Acid 1197-18-8 ORAL

(LD50):

Acute:

>10000

mg/kg

[Mouse].

--

64 5-(1-

Carboxyethyl)-2-

Phenylthio-

Phenylacetic Acid

83237-49-4 -- --

65 Zaltoprofen 74711-43-6 300

mg/kg

--

TOTAL 21.88 120 141.88

LIST OF RAW MATERIALS

• EXISTING

SR.

NO. Name of Raw Materials

CAPACITY

(KGS/Month)

1. Betamethasone 42

2. 1,3 dibromo propene 1231

3. 1,4 dioxane 621

4. 16 Hydroxy prednisolone 33

5. 19 hydroxy-4-androst-3,17-dione 179

6. 5 tr(Tetraene Acetate) 103

7. 8 dm (16 alphamethyl 17,21 dihydroxy 9,11 epoxy Pregna 1,4 diene

3,20 dione) 24

8. Acetic Acid 26

19

9. Acetic Anhydrate 31

10. Acetone 894

11. Acetylene gas 91

12. Androstenedione 212

13. Bep (betamethasone-17-propionate) 52

14. Betamethasone 192

15. Butyaldehyde 13

16. Charcoal 64

17. Chloroform 469

18. Comium trioxide 61

19. Cromic Acid 9

20. db 11(16alphamethyl 17,21 dihydroxy 9,11 epoxy Pregna 1,4 diene

3,20 dione) 29

21. Dexamethasone 42

22. Diflorasone 32

23. Dimethyl foramide 1230

24. Ethyl acetate 7

25. Formaldehyde 4681

26. Furoyl chloride 11

27. HCl (Hydrochloric Acid) 1826

28. Hexane 35

29. hf acid (Hydrofluoric Acid) 351

30. hyflow 76

31. Isopropyl alcohol 85

32. Isopropyl ether 56

33. K2CO3 (Potassium carbonate) 267

34. Lithium chloride 137

35. Mdc (Methylene Dichloride) 842

36. Melamine 2416

37. Methanol 1436

38. Mibk (methyl isobutyl ketone) 225

20

• PROPOSED

39. MSC (Methane Sulfonyl chloride) 109

40. Pet. Ether 81

41. Potassium carbonate 4406

42. Potassium hydroxide 1040

43. Ppc (Pyrophosphoryl Chloride) 109

44. Prednisolone 59

45. Propionic anhydride 83

46. Pthalamide 3846

47. Ptsc (p-Toluene Sulphonic Acid) 26

48. Pyridine 324

49. Sodium borohydrate 22

50. Sodium hydroxide 271

51. Sodium metabisulphide 2265

52. Sulfuric Acid 398

53. TEA (Tri ethyl Amine) 43

54. TEOF (Triethyl ortho fromate) 129

55. Tetrahydrofuran 260

56. Tmop (Trimethyl Orthopropionate) 56

57. Triethyl orthopropionate 86

58. Triethyl orthobutyrate 25

SR.

NO. Name of Raw Materials

CAPACITY

(MT/Month)

Proposed

GROUP-A

1. Acebrofylline

1. Acefylline 11.85

2. Toluene 70.50

3. Ambroxol base 18.90

4. DMF 30.00

21

2. Ambroxol Hydrochloride

1. Toluene 72.00

2. 2 Amino 3,5 dibromo benzaldehyde 22.20

3. Trans-4-Amino cyclohexanol 9.00

4. Methanol 72.00

5. Sodium Borohydride 3.60

6. Activated Carbon 1.20

7. Methanolic HCl 12.90

3. Amlodipine Besylate

1. Phthaloyl Amlodipine 32.63

2. Mono Methyl Amine 50.25

3. Methanol 131.25

4. Ethyl Acetate 92.63

5. Benzene Sulfonic Acid 11.25

6. Carbon 2.25

4. Bupropion Hydrochloride

1. Toluene 75.00

2. 3-Chloro-2’-Bromo Propiophenone 30.00

3. tert butyl amine 10.50

4. 20% Methanolic HCl 24.30

5. Iso Propyl Alcohol 60.00

6. Carbon 0.90

5. Celecoxib

1. 4 SPH 21.00

2. Dione Derivative 19.50

3. Toluene 84.00

4. Carbon 1.50

6. Doxofylline

1. Theofylline 26.10

2. 2-Bromomethyl-1,3-dioxolane 24.30

3. Sodium Carbonate 8.40

22

4. Dimethyl Formamide (DMF) 72.00

5. Carbon 0.30

7. Drotaverine Hydrochloride

1. 3,4-Diethoxy phenylacetic acid 16.50

2. 3,4-Diethoxy phenyl ethyl amine 15.00

3. Toluene 90.00

4. Sodium Hydroxide 1.50

5. Phosphorous oxychloride 13.80

6. IPA 45.00

GROUP-B

8. Etoricoxib

1. Ketosulfone 25.50

2. DMF 75.00

3. CDT Salt 27.90

4. Potassium tert Butoxide 12.90

5. Toluene 60.00

6. Acetic Acid 9.00

7. IPA 45.00

8. Carbon 0.90

9. Flubiprofen

1. 2,4-Difluoronitrobenzene 26.40

2. Diethyl methyl malonate 28.50


4. Dimethylformamide 29.40

5. Toluene 161.40

6. Palladium Catalyst 0.60

7. Hydrogen 1.50

8. Methanol 86.40

9. Benzene 19.80

10. Copper Powder 4.50

11. Sodium Nitrite 14.70

23

12. Acetic Acid 13.50

13. Conc HCl 80.40

14. Carbon 0.30

10.Glibenclamide

1. Sulfonamide Derivative 24.30

2. Ammonia 37.50

3. Cyclo Hexyl Isocyanate 8.40

4. Acetone 243.90


6. Conc HCl 13.20

7. Carbon 1.50

11. Phenazopyridine Hydrochloride

1. Aniline 12.38

2. Conc HCl 19.50


4. 2,6 Diamino Pyridine 13.88

5. Acetone 75.00

6. HCl gas 5.10

12. Phenyl Ephrine Hydrochloride

1. m Hydroxy Acetophenone 33.90


3. Bromine 42.00

4. Toluene 169.50

5. N Methyl benzyl Amine 54.90

6. IPA.HCl 31.50

7. Palladium carbon 1.20

8. Methanol 100.50

9. Liq Ammonia 60.00

10. L Tartaric Acid 33.90

11. IPA 69.90

12. Acetic Anhydride 33.00

24

13. Sulfuric Acid 7.20


15. Carbon 0.90

13. Quetiapine Fumarate

1. Dibenzo-1,4-thiazepine one 17.40

2. Thionyl chloride 15.00

3. Toluene 75.00

4. Piperazin ethoxy ethanol 13.80

5. Ethanol 90.00

6. Fumaric Acid 4.50

7. Acetic Acid 3.00

14. Telmisartan

1. 1,7'-Dimethyl-2'-propyl-2,5'-bibenzimidazole 19.50

2. Methyl 4'-(bromomethyl) biphenyl-2-carboxylate 19.80

3. Sodium carbonate 9.60

4. DMF 120.00

5. Methanol 99.00

6. Sodium hydroxide 3.60

7. Conc HCl 11.40

8. Carbon 0.60

15. Valsartan

1. Bromo OTBN 22.50

2. L Valine 10.50

3. Methanol 60.00

4. Thionyl Chloride 12.45


6. Conc HCl 17.25

7. Acetone 90.00

8. Valeryl Chloride 10.88

9. MDC 75.00

10. Sodium Azide 9.75

25

11. Caustic lye 3.75

12. Carbon 1.50

GROUP-C

16. Bisoprolol Fumarate

1. 4-hydroxy benzyl alcohol 3.75

2. 2- Isopropoxy ethanol 3.50

3. Amberlyst-15 1.25



6. Epichlorohydrin 2.88

7. Toluene 27.50

8. Sodium borohydride 0.38

9. Methanol 31.25

10. Isopropyl amine 2.75

11. MDC 21.25

12. Acetone 40.00

13. Fumaric Acid 3.25

14. Carbon 0.30

17. Brimonidine Tartrate

1. Chorobenzene 80.00

2. 5-Bromo-6-thiouredo quinoxaline 8.00

3. Ethylene diamine 5.00

4. Isopropyl alcohol 20.00

5. Conc HCl 25.00

6. Caustic Lye dilute 40.00

7. Methanol 90.00

8. L Tartaric Acid 5.50

9. Carbon 1.00

18. Capacitabine

1. 5 Fluoro Cytosine 5.00

2. MDC 75.00

26

3. 5-Methyltetrahydrofuran-2,3,4-triyl triacetate 10.75

4. Methanol 90.00

5. n Pentyl Chloroformate 11.25

6. Conc HCl 8.00

7. Caustic lye 5.00

8. Carbon 0.50

9. Ethyl acetate 62.50

10. n Heptane 2.50

19. Cinacalcet Hydrochloride

1. Trifluoro methyl Cinnamic acid 7.50

2. Methanol 30.00

3. Raney Nickel 1.30

4. Toluene 15.00

5. Boric Acid 0.30

6. Naphthyl ethyl amine 5.80


8. MDC 7.50

9. Conc HCl 12.50

10. Carbon 0.80

20. Donepezil Hydrochloride

1. 2-[(1-Benzyl-4-piperidyl)methyl]-5,6-dimethoxy inden-1-one 10.75

2. Methanol 55.00

3. Palladium Carbon 0.55

4. Hydrogen 2500 M3

5. Toluene 37.50

6. IPA 20.00

7. Carbon 0.25

8. IPA HCl 9.15

21. Gemcitabin Hydrochloride

1. Dibenzoyl Lactum 32.50


27

3. Sodium bis(2-methoxyethoxy)- aluminumhydride 17.50

4. Tri ethyl amine 5.00

5. Methane Sulfonyl Chloride 32.50

6. Acetyl Cytosine 13.30

7. Trimethylsilyl chloride 2.30

8. Toluene 82.50

9. Liq Ammonia 17.50

10. Conc HCl 33.80

11. Acetone 25.00

12. Carbon 0.50

22. Glimepiride


2. Trans Iso Cyanate 6.00

3. Acetone 100.00

4. Potassium Carbonate 7.50

5. Methanol 40.00

6. Conc HCl 16.30

7. Carbon 2.50

23. Ivabradine Hydrochloride


2. Acetone 20.00

3. IDDB 9.00

4. MBC.HCl 6.00

5. Toluene 30.00

6. Palladium on Carbon 0.80

7. IPA 12.00

8. Conc HCl 15.00

9. Methanol 60.00

10. Carbon 1.00

24. Nebivolol Hydrochloride

1. 6-Fluoro-2-(oxiran-2-yl)-3,4-dihydro-2H-chromene 10.00

28

2. Benzyl amine 3.25

3. TBAB 1.00

4. Toluene 30.00

5. IPA 37.50

6. Palladium on Carbon 0.25

7. Methanol 40.00

8. Carbon 0.50

9. HCl Gas 1.75

25. Pirfenidone

1. Di methyl formamide 22.50

2. Bromo benzene 10.80


4. 5-Methyl-1H-pyridin-2-one 1.90

5. Copper Oxide 7.00

6. Toluene 16.00


8. Conc HCl 9.00

26. Sofosbuvir

1. Phenyl Phosphorodichloridate 5.25

2. (S)-Isopropyl 2-Amino propanoate hydrochloride 4.50

3. Potassium carbonate 4.25

4. DMF 20.00

5. TBAB 0.50


7. 1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-

ethyltetrahydro-furan-2-yl)pyrimidine-2,4(1H,3H)-dione 6.25

8. Methanol 25.00

9. Carbon 0.50

27. Terbinafine Hydrochloride

1. Naphthyl methyl chloride 6.25

2. Methyl amine 4.00

29

3. Toluene 30.00

4. 1 Chloro 6,6 Dimethylhept-2-en-4-yne 5.75


6. DMF 37.50

7. IPA 20.00

8. HCl gas 2.25

9. Carbon 0.50

28. Ursodeoxycholic acid

1. 3-hydroxy-7-ketocholanic acid 10.80

2. Butanol 22.50

3. Sodium metal 1.50

4. Phosphoric acid 85% 9.30

5. Imidazole 2.30

6. Methanol 47.50


8. Conc HCl 10.50

GROUP-D

29. 2 Amino Phenyl phenyl Sulfide

1. Thio Phenol 25.60

2. 2 Nitro Chloro Benzene 34.40

3. Caustic Flakes 11.20

4. Raney Nickel 0.80

5. Methanol 160.00

30. 2-Amino-3,5-dibromobenzaldehyde

1. Methyl Anthranilate 24.00

2. Methanol 216.00

3. Bromine 25.60

4. THF 68.00


6. Toluene 96.00

7. Manganese dioxide 23.20

30

31. Dibenzo[b,f][1,4]Thiazepin-11(10H)-One

1. 2 Amino phenyl phenyl sulfide 38.00

2. Poly Phosphoric Acid PPA 120.00

3. Ethyl Chloro formate 25.20

32. 4 Methyl Acetophenone

1. Acetyl Chloride 26.00

2. Toluene 48.00

3. Aluminum Chloride 64.00

4. Conc HCl 28.00

33. 2-Chloro-1,3-bis(dimentylamino)trimethinium hexafluorophosphate

1. Dimethylformamide 14.40

2. Chloroacetyl chloride 16.00

3. Phosphorus Oxychloride 22.00


5. Hexafluoro phosphoric acid 36.00

34. 2,3-Dibenzoyl-D-Tartaric acid (DBDT)

1. Benzoyl Chloride 35.60

2. D Tartaric Acid 21.20

3. Toluene 60.00

35. Ethyl Trifluoro Acetate

1. Trifluoro Acetic Acid 34.40

2. Ethanol 20.00


4. Sulfuric Acid 4.80

36. m Phenoxy benzyl alcohol

1. m Phenoxy Benzaldehyde 39.92

2. Nickel Catalyst 0.20

37. p Methoxy Phenyl Acetonirile

1. 4 Methoxy Benzaldehyde 41.60

2. Nickel Catalyst 0.80

3. Hydrogen gas 11200 M3

31

4. Nitrogen 800 M3

5. Conc HCl 96.00

6. Toluene 80.00

7. Sodium Cyanide 14.40

8. Sodium Chloride 4.80

38. Phthaloyl Amlodipine

1. Ethyl-4-(2-phthalimido) ethoxy acetoacetate 28.00

2. o Chloro Benzaldehyde 13.20

3. Acetic Acid 4.00

4. Methyl 3 Amino Crotonate 11.20

5. Methanol 120.00

39. Sulfanilamide

1. Acetanilide 36.00

2. Chloro Sulfonic Acid 62.40

3. Ammonia Solution 116.00

4. Conc HCl 48.00

5. Soda Ash 22.40

40. 3-Trifluoromethyl Cinnamic Acid

1. 3 Trifluoromethyl Aniline 32.00

2. Conc HCl 53.20


4. Acrylonitrile 11.60


6. Conc Sulfuric Acid 14.00

GROUP-E

41. Glipizide


2. Cyclo Hexyl Iso Cyanate 3.50


4. Acetone 80.00

5. Methanol 60.00

32

6. Carbon 0.25

7. Conc HCl 16.00

42. Modafinil

1. 2-[(Diphenyl methyl)sulfanyl] acetamide 12.00

2. Acetic Acid 16.25

3. Hydrogen Peroxide 6.75

4. Methanol 37.50

43. Mycophenolate Mofetil

1. Mycophenolic acid 7.63

2. 2 Morpholinoethanol 5.75

3. PTSA 0.38

4. Ethanol 37.50

44. Tadalafil

1. Carboxylate Intermediate 11.38

2. Methanol 50.00

3. Methyl Amine 14.75

45. Tranexamic Acid

1. Benzoate derivative 14.50

2. Sodium Methoxide 4.13

3. Methanol 45.00

4. Ruthenium 0.25

5. Hydrogen gas 7500 M3

6. Nitrogen 750 M3

7. Potassium hydroxide 5.25

8. Conc HCl 16.25

9. Carbon 0.50

46. 5-(1-Carboxyethyl)-2-Phenylthio-Phenylacetic Acid

1. 2 Phenylthio 5 Propionyl Phenyl Acetic Acid 10.70

2. Toluene 40.00

3. TriethylFormate 7.70

4. Zinc Dust 1.00

33

5. Bromine 7.50

6. Carbon 0.30

47. Zaltoprofen

1 5(1-Carboxyethyl)-2-Phenylthio-phenylacetic Acid 11.67

2 Poly Phosphoric Acid 30.00

3 EDC 23.33

4 Carbon 0.67

34

ANNEXURE – 2

PLANT LAYOUT

TOTAL PLOT AREA : 33081 m

2

35

ANNEXURE – 3

MANUFACTURING ACTIVITIES

EXISTING:

DESCRIPTION OF MANUFACTURING PROCESS WITH FLOW DIAGRAM:

1) Ethisterone

BRIEF PROCESS:

4- Androst-3,17- dione(4AD) reacted with Acetylene gas in presence of potassium

hydroxide and 1,4-dioxane as a solvent gives Ethisterone.

Chemical Reaction :

Mass Balance:

Sr. No. Input Kg Output Kg

1 1,4-Dioxane 432.6

Ethisterone 33.0

2 Isopropyl Alcohol 54.6

Waste water to ETP 250

3 Potassium Hydroxide 148.0

Mother Liquor 1250

4 Androstenedione 35

ML to ETP 360

5 Water 750

Evaporate loss 27

6 Acetylene gas 15

Filtration Loss 5.2

7 HCl 240

8 Water for washing 250

TOTAL 1925.2 TOTAL 1925.2

36

2) Nandrolone

BRIEF PROCESS:

19-Hydroxy-4- androst 3, 17-dione reacts with chromium trioxide in presence of sulphuric

acid it gives acid derivatives. This derivatives further react with Hydrochloric acid and

gives 19-Nor-4-androst-3,17-dione.It is react with Trimethyl ortho formate in presence of

sulphuric acid it gives 3-methoxy derivateive. Further reaction of this derivative with

sodium borohydride and Hydrochloric acid get Nandrolone.

Chemical Reaction :

Mass Balance:


1 19 Hydroxy 10

Nandrolone

5.6

2 Chloroform 177.6

Waste water to ETP 662.71

3 Comium trioxide 3.4

Aqueous Layer to ETP 129.0

4 Water 669.16

Mother liquor to ETP 153.24

5 Sulphuric Acid 14.59

Distillation loss 13.5


Evaporates Loss 14.4

7 Methanol 114.42

Chloroform recovery 172

37

8 HCl 2.25

9 19. Nor 7.5

10 DMF 31.58

11 TEOF 7.2

12 TEA 1.52

13 Sodium borohydride 1.23

TOTAL 1150.45 TOTAL 1140.95

3) Betamethasone Valerate

BRIEF PROCESS:

Betamethasone reacts with Trimethyl ortho valerate in methylene dichloride as a solvent

in presence of catalyst which is further hydrolyzed in Acetone with dil Acid to get

Betamethasone Valarate crude. Betamethasone Valarate crude purify in Methylene

dichloride and Methanol to get Pure Betamethasone Valarate.

Chemical Reaction :

Mass Balance:


1 Betamethasone 9.0

Betamethasone Valarate 2nd

Crop 1.5

2 PTSA 0.41

Betamethasone Valarate 1st

Crop 10

3 Ethyl Acetate 1.5

Waste Water to ETP 827

4 TMOV 7.5

Mother Liquor 80

5 MDC 91.5

Solvent Recovery 75

38

6 Pet.Ether 63.7

Solid Waste 5.73

7 Acetone 108

Residue 0.5

8 Charcoal 0.5

Loss 2.5

9 Sulfuric Acid 0.120

10 Water 700


TOTAL 1002.23 TOTAL 1022.23

4) BUDESONIDE

BRIEF PROCESS:

16 Hydroxy Prednisolone (16 HPN) reacted with Butaralehyde in presence of catalyst gives

Budesonide crude.This is purify in Methanol to get Budesonide Pure.

Chemical Reaction :

Mass Balance:


1 16 HPN

(16 Hydroxy perdnisolone) 5.0

Budesonide (Dry ) 4.0

2 1,4-Dioxane 40.0

Budesonide 2nd

Crop 0.5

3 Butyraldehyde 2.0


4 Water 220

Filtration Loss 5.0


Solvent recovery 93

6 Budesonide crude 5.0

Solid Waste (Hyflo +Charcoal) 1

39

7 Methanol 50.0

Distillation Loss 2

8 Charcoal 0.5

Loss 2.5

9 Hyflo 0.5

Residue 1.0


5) MOMETASONE FUROATE

BRIEF PROCESS:

8DM react with Paratoluene sulphonyl chloride it gives 21-chlorinated product,which

react with furoyl chloride in presence of Triethyl amine to get Momestasone furoate

crude. This is purify in Chloroform- Methanol gives Mometasone Furotate pure.

Chemical Reaction :

Mass Balance:


1 MDC 131.6

Mometasone Furoate 2.7

2 8DM 3.0

2ND crop of MMF 1.0

40

3 PTSC 3.0

Waste water for ETP 90

4 Triethyl Amine 1.9

Aqueous layer to ETP 69

5 Furoyl Chloride 1.3

Solvent Recovery 131

6 HCl 10.9


7 Water 52.5

Evaporation loss 24.5


Recovery of solvent MDC 40

9 MDC Layer (1st

stage) 44

Mother liquor ETP 1.3

10 Methanol 40

Filtration Loss 2.3

11 Hexane 4.3

Solid Waste 1.3

12 Crude MMF 1st

Crop 4.0

13 2nd

MMF Crude Crop 0.4

14 Charcoal 0.3

15 Hyflo 1.0


6) TRIAMCINOLONE

BRIEF PROCESS:

STR is reacted with Hydrofluric acid gives Trimcinolone Crude. This on further purification

in mix solvents gives pure Trimcinolone.

Chemical Reaction :

41

Mass Balance:


1 STR 5

Triamcinolone 4.5

2 HF acid 17


3 K2CO3 40

Mother Liquor to ETP 549

4 Water 775

Distillation Loss 30

5 DMF 38

Filtration Loss 6.0

6 Charcoal 0.5

Solvent Recovery 37

7 Hyflow 0.5

Solid Waste (Hyflo + Charcoal) 1.0


Loss 22.5

TOTAL 1006 TOTAL 1006

7) BETAMETHASONE DIPROPIONATE

BRIEF PROCESS:

Betamethasone reacts with Triethyl ortho propionate in Dimethyl formamide as a solvent

in presence of catalyst which is further hydrolyzed in same solvent with dil acid to get

Betamethasone -17 Propionate. Further Reaction occurs with pyridine and propionic

Anhydride to get Betamethasone Dipropionate Crude. This is purified with activated

charcoal in methelyne dichloride and Methanol mixture to get pure Betamethasone

Dipropionate.

Chemical Reaction :

42

Mass Balance:


1 Sulfuric acid 1.0

Dry BDP Pure 10.0

2 Betamethasone 10.0

Dry BDP 2nd

Crop 0.5

3 Triethyl Orthopropionate 8.0


4 DMF 32.0

Solvent Recovery 37

5 Water 325.0

Recovery Pyridine 24

6 Dry BEP 11.0

Filtration loss 15.5

7 1 Pyridine 25.0

Evaporated loss 10.0

8 2 Propionic anhydride 11.0

Solid Waste (Hyflo +Charcoal) 10.0

9 Ice water 200.0

Recovery (Methanol +MDC) 89.0

10 Water for washing 50.0

Loss 1.5

11 HCl 30% 2.0

Mother Liquor to insulation 1.5

12 Dry BDP Crude 12.0

43

13 Methanol 79.0

14 MDC 13.0

15 Charcoal 1.0

16 Hyflo 1.0

TOTAL 781 TOTAL 781

8) CLOBETASOLE PROPIONATE

BRIEF PROCESS:

Betamethasone reacts with Triethyl ortho propionate in Dimethyl formamide as a solvent

in presence of catalyst which is further hydrolyzed in same solvent with dil acid to get

Betamethasone -17 Propionate. Betamethasone 17-Propionate reacted with Methane

sulphonyl chloride gives Methane sulphonyloxy derivatives. This derivative refluxed with

chlorinated salt gives Clobetasol propionate crude. Crude clobetasol propionate purify in

Methylene dichloride and Methanol to get pure clobetasol propionate.

Chemical Reaction :

44

Mass Balance:

Sr.

No. Input Kg Output Kg

1 Sulfuric acid 1.0

Clobetasole Propionate 1st

crop 9.0

2 Betamethasone 30

Clobetasole Propionate 2nd

crop 0.5

3 Triethyl Orthopropionate 8.0


4 DMF 75.7

DMF Recovery 72.95

5 Water 695

Triethyl Orthopropionate

recovery 32.25

6 BEP (1ST

Stage) 11

Evaporated loss 25.0

7 Pyridine 43


8 MSC 8

Pyridine recover 42.0

9 2nd

Stage 11.5

Solid Waste

(Hyflo +Charcoal+ Solvent) 3

10 Chloride 10

Distillation Loss 3

11 Crude Clobetasole propionate

(3rd

stage) 12

Solvent Recover 91

12 Methanol 79

Filterate to ETP 1.0

13 MDC 14

14 Charcoal 0.5

15 Hyflo 0.5



9) TRIAMCINOLONE ACETONIDE

BRIEF PROCESS:

5TR is reacted with Hydrofluoric acid and Acetone gives Triamcinolone Acetonide Crude.

This on further purification in mix solvents gives pure Triamcinolone Acetonide.

Chemical Reaction :

45

Mass Balance:

Sr.


1 HF Acid 17

Triamcinolone Acetonide 4.5

2 5TR 5

Triamcinolone Acetonide 2nd

crop 0.5

3 Acetone 11


4 Water 300

Mother liquor to ETP 359

5 Water for Washing 70

Filtration Loss 10

6 Potassium carbonate 40

Distillation Loss 7

7 TMCA Crude 6

Drying Loss 8.0

8 Methanol 47

Solvent recovery 128

9 MDC 88

Solid Waste (Hyflo +Charcoal) 1.0

10 Charcoal 0.5

11 Hyflo 0.5

12 Isopropyl Ether 4.0


10) SULPHONATED MELAMINE FORMALDEHYDE CONDANSATE SOLUTION

BRIEF PROCESS:

Formaldehyde, Melamine, Sodium metabisulphate and water react in presence of

sulphuric acid and gives Sulphonate melamine formaledehyde condensate solution.

46

Chemical Reaction :

Mass Balance:

Sr.


1 D.M.Water 840

Sulphonated Melamine

Formaldehyde Condansate

Solution

2119

2 Formaldehyde 620

3 Sodium Hydroxide lye 25

4 Melamine 320

5 Sodium Metabisulphate 300

6 Sulfuric Acid 14


11) HALOBETASOL PROPIONATE

BRIEF PROCESS:

Diflorasone reacts with Triethyl Ortho Propionate in Dimethyl formamide as a solvent in

presence of catalyst which is further hydrolyzed in same solvent with dil Acid to get

47

Diflorasone -17 Propionate. Diflorasone 17-propionate reacted with Methane sulphonyl

chloride gives Methane sulphonyloxy derivatives. This derivative refluxed with chlorinated

salt gives Halobetasol propionate crude. Crude Halobetasol propionate purify in

Methylene dichloride and Methanol to get pure Halobetasol propionate.

Chemical Reaction :

Mass Balance:

Sr.


1 Sulfuric Acid 1.0

Halobetasole Propionate 1st

crop 9.0

2 Diflorasone 10.0

Halobetasole Propionate 2nd

crop 0.5

3 Triethyl orthopropionate 8.0


4 DMF 75.7

DMF Recovery 72.5

5 Water 695

TEOP Recovery 7.5

6 Water for Washing 80.0

Pyridine recovery 42

7 1st

Stage 11.0

Solvent recovery 92

48

8 Pyridine 43.0

Evaporation loss 42.25

9 MSC 8.0


10 2nd

Stage 11.50


11 Lithium Chloride 10

Solid waste

(Hyflo+ Charcoal+solvent) 2.0

12 3

rd Stage (Crude Halobetasole

propionate) 12

Residue to ETP 1.0

13 Methanol 79

14 MDC 14

15 Charcoal 1.0

16 Hyflo 1.0


12) DEXAMETHASONE SODIUM PHOSPHATE

BRIEF PROCESS:

Dexamethasone is reacted with Pyrophosphoryl Chloride in presence of catalyst and

further neutralized by addition of alkali solution to get Dexamethasone sodium

phosphate. This is further purified with activated charcoal and proper organic solvent to

get Dexamethasone Sodium phosphate.

Chemical Reaction :

49

Mass Balance:

Sr.


1 Dexamethasone 5.0

Dexamethasone sodium

phosphate (DSP) 1st crop

5.75

2 Tetrahydofuran 31

Dexamethasone sodium

phosphate (DSP) 2nd

crop 0.25

3 PPC 4

Mother liquor for next batch 1.750

4 Water 125



Filtration loss 1.5

6 1st

stage 6

Drying loss 6.0

7 Methanol 24

Solvent recovery 95.25

8 Charcoal 0.5

Solid waste (Hyflo +Charcoal) 1.0

9 Sodium hydroxide 0.5

10 Hyflo 0.5

11 Acetone 40


13) CLOBETASONE BUTYRATE

BRIEF PROCESS:

Betamethasone reacts with trimethyl orthobutyrate in presence of catalyst then further

process with acetone gives Betamethasone-17-butyrate.This on further reaction with

methane sulphonyl chloride gives Betamethasone-17-butyrate-21-mesylate which on

further reaction with dimethyl formamide and Lithium Chloride followed by oxidation

with Chromic acid gives Clobetasone Butyrate. This is further purified with methanol and

MDC.

Chemical Reaction :

50

Mass Balance:

Sr.



Clobetasone Butyrate 1st crop 9.0

2 Betamethasone 10

Clobetasone Butyrate 2nd

crop 0.5

3 Trimethyl orthobutyrate 8.0

Evaporation Loss 44.25

4 Dimethyl formamide 75.7


5 Water 901

Filtration loss 12


Solid waste 2

7 1st

Stage 11

Solvent recovery

(MDC +Methanol) 328

8 Pyridine 43


9 MSC 8

Drying Loss 31.25

51

10 2nd

Stage 11.5

Residue 1.0

11 Lithium chloride 10

12 3rd

stage 12

13 Cromic Acid 3.0

14 Acetone 120

15 4th

Stage 11

16 Methanol 79

17 MDC 14

18 Charcoal 1.0

19 Hyflo 1.0


14) BECLOMETHASONE DIPROPIONATE

BRIEF PROCESS:

DB11 is reacted with hydrochloric acid and acetic acid at lower temperature to give

Beclomethasone Base. Further Beclomethasone reacts with Triethyl ortho propionate in

Dimethyl formamide as a solvent in presence of Catalyst which is further hydrolyzed in

same solvent with dil acid to get Beclomethasone-17-Propionate.Further Reaction occurs

with pyridine and propionic Anhydride to get Beclomethasone Dipropionate Crude.This is

purified with activated charcoal in methelyne dichloride and Methanol mixture to get

pure Beclomethasone Dipropionate.

Chemical Reaction :

52

Mass Balance:

Sr.


1 Hydrochloric Acid 60

BMD 1st

Crop 10.0

2 Acetic Acid 20

BMD 2nd

Crop 0.5

3 DB11 10


4 Water 525

Mother Liquor to ETP 316.5

5 Potassium Hydroxide 50


6 1st

Stage 10.5

Drying loss 8.5

7 TMOP 8.0


8 DMF 31.5



Solid waste (Hyflo+ Charcoal) 3

10 Pyridine 25

11 Propionic Anhydride 61

53

12 2nd

Stage 11

13 Ice+ Water 200

14 HCl 29.5

15 Crude dry BMD (3rd

Stage) 12

16 Acetone 70

17 Charcoal 1.0

18 Hyflo 1.0


15) PREDNISOLONE SODIUM PHOSPHATE

BRIEF PROCESS:

Prednisolone is reacted with Pyrophosphoryl Chloride at low temperature to give

Prednisolone Phosphate (Hydro).Which on treatment with alkali gives crude Prednisolone

Sodium Phosphate.This is further purified with mix solvents.

Chemical Reaction :

Mass Balance:

Sr.


1 Prednisolone 10

Prednisolone Sodium

Phosphate 10

2 THF 110


3 PPC 14


4 Water 147.5

Distillation loss 21

54



6 MIBK 75

Filtration loss 3

7 NaOH 24.5

Recovery Methanol+water 42

8 HCl 17

Evaporation loss 4

9 Methanol 60

Solid waste 2

10 Hyflo 1

Residue 7

11 Charcoal 1

12 Acetone 96

TOTAL 586 TOTAL 586

16) BEATMETHASONE SODIUM PHOSPHATE

BRIEF PROCESS:

Beatmethasone is reacted with Pyrophosphoryl Chloride in presence of catalyst and

further neutralized by addition of alkali solution to get Betamethasone sodium phosphate.

This is further purified with activated charcoal and proper organic solvent to get

Betamethasone Sodium Phosphate.

Chemical Reaction :

Mass Balance:

Sr.


1 Betamethasone 5.0

Beatmethasone sodium

phosphate 1st crop

5.75

2 Tetrahydrofuran 31.0

Beatmethasone sodium

phosphate 2nd

crop 0.250

55

3 PPC 4.0


4 Water 125

Mother Liquor for next batch 1.750


Solvent Recovery 90.75

6 1st

Stage 6.0

Solid Waste (hyflo+Charcoal) 1.0

7 Methanol 24

Filtration loss 1.5

8 Charcoal 0.5

Drying loss 7.0


10 Hyflo 0.5

11 Acetone 40.0

TOTAL 296 TOTAL 296

17) N-(3 BROMO PROPYL PHTHELIDE)

BRIEF PROCESS:

Phthalimide is reacted with 1.3 dibromopropen in presence of potassium carbonate get

N-(3 bromo propyl phthelide).This is further purified with proper organic solvent to get N-

(3 bromo propyl phthelide).

Chemical Reaction :

Mass Balance:

Sr.


1 Phthalimide 250

N-(3-bromo propyl phthelide

1st crop

300

2 1,3-Dibromo propen 1700

N-(3-bromo propyl phthelide

2nd

crop 25

3 Potassium Carbonate 250


56

4 Water 100

Potassium carbonate solution

for next batch 350


1,3 dibromo propen recover 1621

6 Acetone 395

Acetone recover 383

7 Methanol 475

Methanol recover 460

Distillation loss 31


18) PREDNISOLONE ACETATE

BRIEF PROCESS:

Prednisolone reacts with Acetic Anhydride in presence of Pyridine which gives

Prednisolone Acetate. This is purified in mix solvents and gets pure Prednisolone Acetate.

Chemical Reaction :

Mass Balance:

Sr.


1 Prednisolone 10

Prednisolone Acetate 1st crop 10

2 Pyridine 49

Prednisolone Acetate 2nd

t crop 0.5

3 Acetic Anhydride 10.8


4 HCl 2.0

Solvent Recovery 205

5 Water 200.0


6 Water for Washing 140.0

Solid Waste 2.0

57

7 Methanol 47.2

Evaporation Loss 17.5

8 MDC 88.2

Filtration Loss 7.4

9 Charcoal 1.0

10 Hyflo 1.0

11 Crude Prednisolone Acetate 11.0


PROPOSED GROUP- A:


1) Acebrofylline

BRIEF PROCESS:

• Charge Toluene and Acefylline in Reactor

• Heat the reaction mass & maintain it

• Charged Dimethyl formamide and Ambroxol Base clear solution in above RM.

• Heat the reaction mass & maintain it. Now slowly cool the RM

• Filter the reaction mass and dry to give Acebrofylline

Chemical Reaction :

58

+

MW 238.20

MW 616.30

Acebrofylline

MW 378.10

Br

Br

NH2

NH

OH

Ambroxol Base

N

N

O

CH3

N

N

O

CH3

O

OH

Acefylline

Br

Br

NH2

NH

OH

N

N

O

CH3

N

N

O

CH3

O

OH

Mass Balance:

Sr. No. Input MT Output MT

1 Acefylline 11.85

Final Product 30.00

2 Toluene 70.50

Toluene Recycle 68.40

3 Ambroxol base 18.90

D M F Recycle 27.60

4 DMF 30.00

Distillation + Drying loss 4.65

Residue 0.60


59

2) Ambroxol Hydrochloride

BRIEF PROCESS:

• Charged 2 Amino 3,5 dibromo benzaldehyde and Toluene in Reactor at RT

• Charged Trans-4-Amino cyclohexanol in above reaction mixture


• Filter the reaction mass and collect the wet material

• Charged Methanol & above wet cake

• Charged Sodium Borohydride & maintain it

• Distill out methanol and charge purified Water

• Filter the reaction mass & collect wet material

• Charge Methanol and above wet cake and Heat the reaction mass to get clear solution

• Charge Activated Carbon slurry & filter it. Collect clear filtrate and charge into the reactor.

• Charge Methanolic Hydrochloric acid & maintain the reaction mass

• Filter the reaction mass wash with methanol and dry to give Ambroxol Hydrochloride

Chemical Reaction:

MW 278.92

Br

OHC Br

NH2

2 Amino 3,5 Dibromo

Benzaldehyde

+

OH

NH2

MW 115.17

trans 4 Amino

Cyclohexanol

MW 376.08

Br

Br

NH2

N

OH

MW 414.56

Br

Br

NH2

NH

OH

MW 376.08

Br

Br

NH2

N

OH

Ambroxol Hydrochloride

ClH

NaBH4

HCl

60

Mass Balance:


1. Toluene 72.00

Final Product 30.00

2. 2 Amino 3,5 Dibromo benzaldehyde 22.20


3. Trans-4-Amino cyclo hexanol 9.00

Methanol Recycle 70.20

4. Methanol 72.00



Residue 2.10

6. Activated Carbon 1.20

Effluent 21.00


Carbon Waste 1.50

8. Water 18.00


3) Amlodipine Besylate

BRIEF PROCESS:

STAGE 1

• Charge Methanol, Phthaloyl Amlodipine and Mono Methyl amine in Reactor.

• Heat the reaction mass under stirring for several times.

• After completion of the reaction, Solvent was removed under vacuum to get crude

material

• The solid was treated with water under stirring and heating. Cool the rm and filter the

solid

• The crude solids are washed with water.

• Dry the product to give White to off white solid.

STAGE 2

• Charge Ethyl acetate and step 1 and in Reactor.

• Charge Benzene Sulfonic acid solution in ethyl acetate in above RM. Heat the mass.

• Heat the reaction mass under stirring for several time.


material.

• The solid was treated with methanol under stirring and heating. Cool the rm and filter

the solid.

• The crude solids are washed with methanol.

• Dry the product to give White to off white solid .

61

Chemical Reaction:

Mono Methyl Amine

4-(2-Chlorophenyl)-3-ethoxycarbonyl-5-methoxy

carbonyl-6-methyl-2-(phthalimidoethoxy)

methyl-1,4-dihydropyridine (Phthaloyl Amlodipine)

MW 538.98

N

H

CH3

H3COOC COOC2H5

Cl

ON

O

O

MW 31.05

3-ethyl 5-methyl 2-[(2-aminoethoxy)

methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydro

pyridine-3,5-dicarboxylate

MW 408.87

N

H

CH3

H3COOC COOC2H5

Cl

ONH2

HCH3 N

O

O

+

2 Methyl-1-isoindole-1,3-dione

MW 161.16

62



pyridine-3,5-dicarboxylate amlodipine Besylate

N

H

CH3

H3COOC COOC2H5

Cl

ONH2

H



pyridine-3,5-dicarboxylate

MW 408.87

N

H

CH3

H3COOC COOC2H5

Cl

ONH2

H+

Benzene Sulfonic Acid

MW 158.17

SO3H

SO3H

.

MW 567.05

Mass Balance:


1 Phthaloyl Amlodipine 32.63

Final Product 30.00

2 Mono Methyl Amine 50.25


3 Methanol 131.25

Ethyl Acetate Recycle 89.25

4 Ethyl Acetate 92.63

Residue 3.38

5 Benzene Sulfonic Acid 11.25

Drying + Distillation loss 12.00

6 Carbon 2.25

Effluent 320.25

7 Water 264.00

Carbon waste 4.13


63

4) Bupropion Hydrochloride

BRIEF PROCESS:

STAGE 1 : 2-(tert-Butylamino)-1-(3-chlorophenyl) propan-1-one bupropion hydrochloride

• Charged Toluene in Reactor at RT.

• Charge 3-Chloro-2’-Bromo Propiophenone in Toluene

• Slowly charged tert butyl amine in about mass at RT

• Heat Reaction Mass to 55-60oC. Maintain this temp for 3-4 hrs

• Add water in above reaction mass and stir for 1 hrs.

• Now cool the reaction mass and separate the organic layer.

• Charged Carbon in above layer and heat it.

• Filter the above Reaction Mass by Sparkler filter.

• Chilled the filtrate and then Charged Methanolic HCl in Reactor at 5-10oC.

• Maintain RM for 3 hrs at same temp.

• Filter the solid mass.

• Charged Iso Propyl Alcohol in Reactor at RT.

• Add solid mass and stir for 2 hrs.

• Filter the solid mass and dry it.

Chemical Reaction:

3 Chloro 2 Bromo Propiophenone Bupropion.HCl

MW 247.52 MW 276.20

Cl

OCH3

Br

(CH3)

3CNH

2

Cl

OCH3

NHCH3

CH3CH3

. HCl

Mass Balance:


1 Toluene 75.00

Final Product 30.00

2 3-Chloro-2’-Bromo Propiophenone 30.00


3 tert butyl amine 10.50

Isopropyl alcohol Recycle 54.30

4 20% Methanolic HCl 24.30


64

5 Iso Propyl Alcohol 60.00

Residue 1.80

6 Carbon

0.90

Effluent 68.40

7 Water 45.00

Carbon Waste 1.20


5) Celecoxib

BRIEF PROCESS:

• Charged water in Reactor at RT.

• Charged 4 SPH and Dione Deri in Reactor

• The reaction mixture was heated and stirred well.

• Cool the RM and Filter the Product.

• Charged Toluene and wet cake in above reactor again.

• Heat the RM and stir well for several time

• The organic layer was washed with water. Add Activated carbon in stirring and heating.

• Filter the RM with Sparkler

• The filtrate was cooled.

• The separated solid was filtered and dried

Chemical Reaction:

SO2NH2

N

N

CH3

CF3

MW 381.37

4-[5-(4-Methylphenyl)-3-(trifluoro methyl) pyrazol-1-yl]benzenesulfonamide celecoxib

Water

Toluene

MW 223.68

4 SPH

SO2NH2

NH

NH2

ClH

CH3

O CF3

O

MW 230.18

Dione deri

+

+ ClH + 2 H2O

MW 36.46 MW 18.01

65

Mass Balance:

Sr.

No. Input MT Output MT

1 4 SPH 21.00

Final Product 30.00

2 Dione Derivative 19.50


3 Toluene 84.00

Distillation + Drying Loss 5.40

4 Carbon 1.50

Residue 1.20

5 Water 48.00

Carbon Waste 2.10

Effluent 55.80


6) Doxofylline

BRIEF PROCESS:

• Charged DMF and Theofylline in Reactor at RT

• Charged 2-Bromomethyl-1,3-dioxolane in above reaction mixture

• The reaction mixture was heated and stirred

• The reaction mixture was cooled.

• Remove excess of solvent under vacuum.

• Now warm the reaction mass and add water in mass.

• Add carbon in above reaction mass and stir well under heating

• Filter the above mass in hot condition

• Cool and then Chilled the reaction mixture

• Maintain same temp for 4 hrs.


Chemical Reaction:

2-Bromomethyl-1,3-dioxolane

MW 180.16

N

N

CH3

N

H

NO

CH3

O

Theofylline

MW 266.25

7-(1,3-Dioxolan-2-ylmethyl)-1,3-dimethyl purine-2,6-dione doxofylline

MW 167.00

+

Br

OO

N

N

CH3

N

NO

CH3

O

O

O

Na2CO

3

NaBr+

MW 102.89

Sodium

Bromide

CO2+

MW 44.01

H2O

MW 18.01

+

66

Mass Balance:

Sr.

No. Input MT Output MT

1 Theofylline 26.10

Final Product 30.00

2 2-Bromomethyl-1,3-

dioxolane 24.30

Dimethyl Formamide (DMF)

Recycle 69.60

3 Sodium Carbonate 8.40


4 Dimethyl Formamide (DMF) 72.00

Effluent 69.60

5 Carbon 0.30

Carbon Waste 0.60

6 Water 44.10


7) Drotaverine Hydrochloride

BRIEF PROCESS:

Stage 1

• Charge Toluene, 3,4-Diethoxy phenylacetic acid, 3,4-Diethoxy phenyl ethyl amine in

Reactor.

• Heat the reaction mass & maintain it as same temp.

• Remove excess of toluene by distillation.

• Now chilled the reaction mass.

• Filter the reaction mass to separate the solid.

• Use wet cake as such for next step

Stage 2

• Charged step 1, Toluene and Phosphorous oxychloride in Reactor

• Heat the reaction mass.

• Charged water in above RM and heat the mass.

• Separate both the layer. Wash organic layer first with dilute Sodium Hydroxide solution

and then with water till pH neutral.

• First cool the mass and then chilling is applied.

• Filter the product.

• Charged IPA in reactor.

• Add above wet cake in IPA and heat the mass.


• Filter the product, and dry.

67

Chemical Reaction:

Stage 1

MW 224.25

3,4 Diethoxy Phenyl Acetic Acid

CH2COOH

OC2H5

OC2H5

CH2CH2NH2

OC2H5

OC2H5

+

MW 209.28

3,4 Diethoxy Phenyl Ethyl Amine

MW 415.52

OC2H5

OC2H5

O

NH

OC2H5

OC2H5

2-(3,4-Diethoxy-phenyl)-N-[2-(3,4-diethoxyphenyl)

-ethyl]-acetamide

Stage 2

68

M W 4 3 3 . 9 6

D r o t a v e r in e H y d r o c h lo r id e

M W 4 1 5 .5 2

O C 2 H 5

O C 2 H 5

O

N H

O C 2 H 5

O C 2 H 5

2 - ( 3 ,4 - D ie t h o x y - p h e n y l ) - N - [ 2 - ( 3 ,4 - d ie t h o x y p h e n y l)

- e t h y l ] - a c e ta m id e

H 5 C 2 O

H 5 C 2 ON H

O C 2 H 5

O C 2 H 5

C lH

Mass Balance:


1 3,4-Diethoxy phenylacetic acid 16.50

Final Product 30.00

2 3,4-Diethoxy phenyl ethyl amine 15.00


3 Toluene 90.00

IPA Recycle 41.10

69

4 Sodium Hydroxide 1.50


5 Phosphorous oxychloride 13.80

Effluent 74.82

6 IPA 45.00

Residue 1.20

7 Water 60.00


GROUP- B:


8) Etoricoxib

BRIEF PROCESS:

• Charged DMF in Reactor at RT.

• Charged Stage 1 and 2-chloro-1,3-bis(dimethyl amino) trimethinium hexaflouro phosphate

salt CDT Salt in above reaction mixture.

• Charged Potassium tetra Butoxide in Reactor at RT

• The reaction mixture was heated and stirred.

• Remove excess of solvent by distillation.

• Charge toluene and acetic acid in above reaction mixture


• Charge water in above reaction mixture

• Separate organic layer and aqueous layer

• Add carbon in Organic layer and stir and filter under heating

• Cool the organic layer and separate the wet cake by filtration

• The separated solid was charged in IPA. Heat and then cool the RM.

• Separate the wet cake by filtration. Dry the Product.

Chemical Reaction :

70

M W 289.35

Ketosulfone

M W 358.84

5-Chloro-6'-m ethyl-3-[4-(methy lsulfonyl)phenyl]-2,3'-bipyridine etoricoxib

O

CH 3

S

O

O

N CH 3

O

CH 3

S

O

N

N CH 3

Cl

CH3

N+

N

CH 3

CH 3

Cl CH 3

PF 6

-

M W 306.62

CD T Salt

+

Mass Balance:


1 Ketosulfone 25.50

Finish Product 30.00

2 DMF 75.00

DMF Recycle 69.90

3 CDT Salt 27.90


4 Potassium tert Butoxide 12.90

IPA Recycle 39.90

5 Toluene 60.00


6 Acetic Acid 9.00

Residue 2.70

7 IPA

45.00

Effluent 115.20

8 Carbon

0.90

Waste Carbon 1.50

9 Water 67.50


71

9) Flurbiprofen

BRIEF PROCESS:

Stage 1

• Charge 2,4-Difluoronitrobenzene in Reactor at RT.

• Charge Diethyl methyl malonate, Sodium Hydroxide and Dimethylformamide in RM at RT.

• Heat Reaction Mass. Maintain this temp for 3 to 4 hrs.

• Charge Toluene in Reactor. Heat to reflux for 30 min.

• Wash the Toluene layer with water.

• Toluene layer was concentrated under pressure to give Diethyl-3-fluoro-(4-nitrophenyl)

methyl propanedioate.

• Resulting intermediate reduction in presence of Palladium Catalyst and Hydrogen gas,

Methanol as solvent.

• After completion of the reaction catalyst was filtered under nitrogen and Methanol layer

was concentrated under reduced pressure to get Stage-1 Compound.

Stage 2

• Charge Stage 1 in Reactor at RT.

• Charge Sodium Nitrile solution, Conc HCl and copper powder in above reaction mass.

• Chilled the Reaction Mass. Maintain this temp for 1-2 hrs.

• Charge slowly Benzene in above reaction mass under chilling condition.

• Now Charged Toluene in above RM under stirring.

• After completion of the reaction Toluene layer was washed with water and concentrated

under reduced pressure to form Stage-2 Intermediate.

Stage 3

• Charge Stage 2 and Sodium Hydroxide solution in Reactor at RT.

• Heat the Reaction Mass. Maintain this temp for 1-2 hrs.

• After completion of the reaction crude solid was isolated by adding Acetic Acid and Conc

HCl to the reaction mass.

• The crude solid was recrystalized in Toluene and Carbon to obtain Finish Product

Chemical Reaction :

Stage 1

+

Diethyl Methyl

Malonate

MW 174.19

NO2

F

F

2,4 Difluoro

Nitrobenzene

MW 159.09

O

O

O

O

CH3

CH3CH3

NH2

F

O

O

O OCH3

CH3

CH3

Stage 1

MW 283.29

NaOH

DMF

Pd/C

Methanol

CH4

72

Stage 2

F

O

O

O OCH3

CH3

CH3

Stage 2

NaNO2

Water

+

Stage 1

MW 283.29

NH2

F

O

O

O OCH3

CH3

CH3

Benzene

MW 78.11 MW 344.37

Stage 3

Finish Product

MW 244.26

NaOH

Conc HCl

Acetic Acid

F

O

O

O OCH3

CH3

CH3

Stage 2

MW 344.37

F

O

OHCH3

+ 2 H2O

Mass Balance:


1 2,4-Difluoronitrobenzene 26.40

Final Product 30.00

2 Diethyl methyl malonate 28.50




4 Di methyl formamide

29.40

Palladium Catalyst Recycle 0.90

5 Toluene

161.40


73

6 Palladium Catalyst

0.60

Residue 3.00

7 Hydrogen

1.50

Carbon waste 0.90

8 Methanol

86.40

Effluent 331.80

9 Benzene

19.80

10 Copper Powder

4.50

11 Sodium Nitrite

14.70

12 Acetic Acid

13.50

13 Conc HCl

80.40

14 Carbon

0.30

15 Water

138.90


10) Glibenclamide

BRIEF PROCESS:

STAGE 1

• Charge Ammonia, Sodium Hydroxide, Sulfonamide derivative and Acetone in Reactor.

• Slowly Charged Cyclohexyl isocyante in Acetone in above solution.

• Heat the reaction mass under stirring for several times.


material

• The solid was treated with water under stirring and heating. Cool the rm and filter the

solid

• The crude solids are washed with chilled methanol.


STAGE 2

• Charge Methanol and step 1 and in Reactor.

• Conc HCl and water solution is slowly charged in above RM. Heat the mass.

• Heat the reaction mass under stirring for several time.

• Cool the reaction mass and filter the solid


• Dry the product to give White to off white solid

74

Chemical Reaction :

Stage 1

Ammonia, Acetone

MW 368.83

CHIC Salt

MW 516.99

NO

Cl

OCH3

O NHSO2NH2

5-Chloro-2-methoxy-N-[2-(4-sulfamoylphenyl)

ethyl]benzamide

+

MW 113.16

Cyclo Hexyl Isocyanate

Cl

OCH3

O NHS

NH

O

OO

NH

. Na

Sodium Hydroxide

75

Methanol

Benzamide 5-chloro-N-[2-[4-[(cyclohexylamino)

carbonyl]amino]sulfonyl]phenyl]ethyl]-2-metoxy glibenclamide

MW 494.00

Cl

OCH3

O NHS

NH

O

OO

NH

Conc HCl

CHIC Salt

MW 516.99

Cl

OCH3

O NHS

NH

O

OO

NH

. Na

Mass Balance:


1 Sulfonamide Derivative 24.30

Final Product 30.00

2 Ammonia 37.50

Acetone 222.90

3 Cyclo Hexyl Isocyanate 8.40

Residue 3.90

4 Acetone 243.90

Drying + Distillation loss 22.50


Effluent 231.00

6 Conc HCl 13.20

Carbon waste 2.40

76

7 Carbon 1.50

8 Water 180.00


11) Phenazopyridine Hydrochloride

BRIEF PROCESS:

Stage 1

• Charged hydrochloric acid, water and Aniline in Reactor at RT. Cool the RM

• Now chilled the RM.

• Charged aqueous Chilled sodium nitrite in above reaction mixture

• Charged 2,6 Diamino pyridine slurry in water in above RM.

• Raise the temp to RT. Stir for some time.

• The separated solid was filtered and dried.

Stage 2

• Charge Stage 1 and Acetone in Reactor at RT. Now cool the RM.

• Charge slowly HCl gas in above mass under chilling condition.

• After completion of the reaction, separate product by filtration.

• Wash the product with chilled Acetone.

• Dry the product.

Chemical Reaction :

Stage 1

NNH2 NH2

MW 109.13

2,6 Diamino Py ridine

NH2

+

MW 93.13

Aniline

NNH2 NH 2

NN

MW 213.23

Step 1

Stage 2

77

NNH2 NH2

NN

MW 249.70

Phenazopyridine Hydrochloride

NNH2 NH2

NN

MW 213.23

Step 1

ClH

Mass Balance:


1 Aniline 12.38

Final Product 30.00

2 Conc HCl 19.50

Acetone Recycle 70.13

3 Sodium Nitrite 9.38

Residue 1.13

4 2,6 Diamino Pyridine

13.88


5 Acetone

75.00

Effluent 83.85

6 HCl gas

5.10

7 Water

60.00


12) Phenazopyridine Hydrochloride

BRIEF PROCESS:

Stage 1

• Charge Ethyl Acetate and m Hydoxy Acetophenone in Reactor at RT. Cool the RM

• Slowly charge Liq Bromine in RM under starring and cooling.

• Maintain this temp for 3 to 4 hrs.

• Charge Toluene in Reactor.

• Wash the Toluene layer with water.

• Toluene layer was concentrated under pressure to Crude stage 1.

Stage 2

• Charge Stage 1 and Toluene in Reactor at RT. Now cool the RM.

• Charge n methyl benzyl amine in above reaction mass.

• Chilled the Reaction Mass. Maintain this temp for 1-2 hrs.

78

• Filter the RM. Separate the wet cake for N methyl benzyl amine recovery.

• Charge slowly IPA.HCl above filtration mass under chilling condition.

• After completion of the reaction separate Stage-2 Intermediate by filtration.

• Wash the product with chilled Toluene.

• Dry the product for next stage reaction.

Stage 3

• Charge Stage 2, Methanol and Palladium carbon in Pressure Reactor at RT.

• Heat the Reaction Mass. Maintain this temp for 4-5 hrs under pressure.

• Cool the RM and filter the mass to separate used Pd/C.

• Remove excess of Methanol under reduced pressure. Add water in RM.

• Crude solid was isolated by adding liq Ammonia in the reaction mass.

• Dry the product for next stage reaction

Stage 4

• Charge Stage 3, IPA and L Tartaric Acid Reactor at RT.

• Charge water in above RM and heat the Reaction Mass. Maintain this temp for 6-8 hrs.

• Cool the RM and filter the Mass - D Salt.

• Take filtrate and adjusted pH to with Liq Ammonia.

• Crude solid A was wash with water and dry it.

• Take D Salt in water and heat it to get clear solution.

• Crude solid was isolated by adding liq Ammonia in the reaction mass

• Dry the product for next stage reaction

• Take Acetic Anhydride and above dry product in reactor and slowly add sulfuric acid.

• Heat the Reaction Mass. Maintain this temp for 8-10 hrs

• Cool the reaction mass and add Liq Ammonia slowly at RT.

• Filter the Solid mass B and dry it.

• Charged Methanol in reactor and add Solid mass A and B. Heat the mass to get clear

solution.

• Give carbon treatment the above solution.

• Charges slowly Methanolic HCl in above filtrate and cool the reaction mass.

• Filter the solid product, wash with chilled Methanol and dry it.

Chemical Reaction:

Stage 1

OH

O CH 2Br

OH

O CH 3

MW 136.15 M W 215.04

3'-H ydroxy Acetoph enone 2-Bromo-3'-H ydroxy Acetoph enone

Br2

+ H Br

79

Stage 2

OH

O

N

CH3

OH

O CH2Br

NHCH3

MW 255.31

MW 121.17

2-Bromo-3'-Hydroxy Acetophenone1-(3-Hydroxyphenyl)-2-[Methyl

(Phenylmethyl)amino]ethanone

MW 215.04

+ HBr

Stage 3

OH

ON

CH3

OH

OHNH

CH3

MW 167.21MW 255.31

1-(3-Hydroxyphenyl)-2-[Methyl

(Phenylmethyl)amino]ethanoneDL Phenyl Ephrine

Hydrogen

CH3

+

MW 92.14

Toluene

Stage 4

OH

OHNH

CH3

OH

NH

CH3

OH

H

MW 167.21

DL Compound

Methanolic HCl

L Tartaric Acid

MW 203.66

Finish Product

. HCl

Mass Balance:


1 m Hydroxy Acetophenone 33.90

Final Product 30.00



3 Bromine 42.00


80

4 Toluene

169.50


5 N Methyl benzyl Amine

54.90

N Methyl benzyl Amine Recycle 24.00

6 IPA.HCl

31.50

Residue 3.00

7 Palladium carbon

1.20


8 Methanol

100.50

Effluent 372.90

9 Liq Ammonia

60.00

Carbon waste 1.50

10 L Tartaric Acid

33.90

Pd/C Recycle 2.40

11 IPA

69.90

12 Acetic Anhydride

33.00

13 Sulfuric Acid

7.20

14 Methanolic HCl

30.00

15 Carbon

0.90

16 Water

112.50


13) Quetiapine Fumarate

BRIEF PROCESS:

• Charged Dibenzo-1,4-thiazepine-11-one and Thionyl chloride in Reactor at RT


• Charged Toluene and water in above reaction mass.

• Cool the RM and stir well for several time.

• Separate Organic layer and aqueous layer.

• Charged Piperazin ethoxy ethanol in above reaction mass and heat for some time.

• Remove excess of Toluene for Organic layer.

• Charged ethanol Acetic Acid and Fumaric Acid in above reaction mass.

• The reaction mixture was heated and stirred well

• Cool the RM and stir well for several time

• The separated solid was filtered wash with water and dried.

81

Chemical Reaction:

Thionyl Chloride

Ethanol

Fumaric Acid

+ H2O

MW 18.02

2-[2-(4-dibenzo [b,f] [1,4]thiazepin-11-yl-1-piperazinyl) ethoxy]-ethanol quetiapine fumarate

MW 227.28

N

H

S

O

Dibenzo[b,f][1,4]Thiazepin-11(10H)-One

N

NH

O

OH+

MW 174.24

2-((2-Piperazin-1-yl)ethoxy)ethanol

NN

O

OH

N

S

H

O

OH

O

OH

H

MW 883.02

Mass Balance:


1 Dibenzo-1,4-thiazepine one 17.40

Final Product 30.00

2 Thionyl chloride 15.00

Toluene 70.80

3 Toluene 75.00

Ethanol 84.90

4 Piperazin ethoxy ethanol 13.80


5 Ethanol 90.00

Effluent 94.50

6 Fumaric Acid 4.50

82

7 Acetic Acid 3.00

8 Water 75.00


14) Telmisartan

BRIEF PROCESS:

Stage 1

• Charged DMF, 1,7'-Dimethyl-2'-propyl-2,5'-bibenzimidazole and Sodium carbonate in

Reactor at RT.

• Charged Methyl 4'-(bromomethyl) biphenyl-2-carboxylate in above reaction mixture.



• Charge water in above reaction mixture


• Cool the Reaction mass and separate the wet cake by filtration

• Wash wet cake by water and finally Dry the Product.

Stage 2

• Charged stage 1, Methanol and Sodium hydroxide in Reactor at RT.


• Charged Carbon and filter the mass by Sparker Filter.


• Charge Dilute HCl in above reaction mixture

• The reaction mixture was stirred.

• Cool the Reaction mass and separate the wet cake by filtration

• Wash wet cake by water and finally Dry the Product.

Chemical Reaction:

Stage 1

83

MW 528.64

Step 1

MW 305.17MW 304.39

N

N

CH3N

H

N

CH3

CH3

+

1,7'-Dimethyl-2'-propyl-2,5'-bibenzimidazole

Br

O

OCH3

Methyl 4'-(bromomethyl)biphenyl

-2-carboxylate

N

N

CH3N

N

CH3

CH3

O

H3CO

84

Stage 2

MW 514.61

Telmisartan

N

N

CH3N

N

CH3

CH3

O

OH

MW 528.64

Step 1

N

N

CH3N

N

CH3

CH3

O

H3CO

Mass Balance:


1 1,7'-Dimethyl-2'-propyl-2,5'-

bibenzimidazole 19.50


2 Methyl 4'-(bromomethyl)

biphenyl-2-carboxylate 19.80

DMF Recycle 116.40

3 Sodium carbonate 9.60


4 DMF 120.00


5 Methanol 99.00

Effluent 76.50


Waste Carbon 0.90

85

7 Conc HCl

11.40

8 Carbon

0.60

9 Water 48.00


15) Valsartan

BRIEF PROCESS:

Stage 1

• Charged Bromo OTBN, Methanol and L Valine in Reactor.

• Charged slowly Thionyl Chloride in above RM at RT.

• Heat to reflux, Distill out Methanol completely

• Charged Ethyl Acetate, Conc HCl and Water in above RM under stirring.

• Cool RM to RT and separate both layer.

• Cool the Ethyl acetate layer.

• Filter the above mass.

• Dissolve wet cake in acetone in hot condition.

• Cool the RM and filter the product and dry it.

Stage 2

• Charged step 1, Valeryl Chloride and MDC in Reactor


• Charged Sodium Azide slowly in above RM under Chilling condition.

• Stir RM at RT for several hrs.

• Charged Conc HCl and water in above mass.

• Separate both layers and charged carbon in above RM.

• Filter the organic layer by sparker filter.

• Adjusted pH 7 to 8 by adding dilute Caustic lye.

• First cool the organic layer and then chilling is applied.

• Filter the product. And dry it.

Chemical Reaction:

Stage 1

86

MW 272.14

Bromo OTBN

MW 117.15

NH2

CH3 CH3

O

OH

+

L Valine

Br

CN

MW 358.86

Step 1

C N

NH

CH3

CH3

O

OCH3ClH

Stage 2

MW 120.58

O

Cl

CH3

+

Valeryl Chloride

MW 435.52

Valsartan

N

CH3

CH3

O

OH

N

H

N

NN

O

CH3

MW 358.86

Step 1

CN

NH

CH3

CH3

O

OCH3ClH

Sodium Azide

Mass Balance:


1 Bromo OTBN 22.50

Final Product 30.00

2 L Valine 10.50


3 Methanol 60.00

MDC Recycle 68.25

4 Thionyl Chloride 12.45


87



6 Conc HCl 17.25

Effluent 189.45

7 Acetone 90.00

Waste Carbon 2.25

8 Valeryl Chloride 10.88

Residue 1.88

9 MDC 75.00

10 Sodium Azide 9.75

11 Caustic lye 3.75

12 Carbon 1.50

13 Water 52.50


GROUP- C :


16) Bisoprolol Fumarate

BRIEF PROCESS:

STAGE 1 :

• Charged 4-hydroxy benzyl alcohol and 2- Isopropoxy ethanol in Reactor at RT

• Amberlyst-15 is added slowly in above reaction mass

• The Amberlyst-15 resin is filtered and washed with 2-Isopropoxy ethanol

• The reaction mixture is treated with sodium carbonate

• The sodium carbonate is filtered and the reaction mixture is taken for distillation to

recover excess of 2-Isopropoxy ethanol to obtain Stage 1

STAGE 2 :

• Charged 20% Sodium Hydroxide solution and stage 1 in reactor.

• The aqueous solution of sodium salt of stage 1 is reacted with epichlorohydrine

• The reaction mixture is then extracted twice with Toluene

• The combined Toluene extract is stirred with solid sodium hydroxide to convert the

intermediate stage

• The reaction mixture is washed with water three times and the Toluene layer is taken for

distillation

• The product is further purified by high vacuum distillation to obtain purified Stage 2

88

STAGE 3 :

• Charged stage 2 and methanol in reactor.

• Catalytic amount of sodium borohydride is added to it in small lots.

• The reaction mixture is stirred for 1 hr and added to cooled isopropyl amine. The reaction

mixture is stirred hrs and heated to reflux

• The excess of Isopropyl amine and methanol is removed by distillation

• The residual oil is taken in dichloromethane and washed thrice with water

• Bisoprolol base is obtained as an oil after removal of solvent by distillation

STAGE 4 :

• Charged Acetone in Reactor at RT

• Charged 1-{4-[(2-Isopropoxyethoxy)methyl]phenoxy}-3-(isopropylamino) Propanol in

above solvent


• Charged Fumaric Acid in above solvent

• The reaction mixture was heated and then add carbon and stirred. filter the RM


• Then Chilled the reaction mixture



Chemical Reaction :

STAGE 1 :

MW 124.14

4 Hydroxy Benzyl alcohol

O

CH3

CH3

OH

MW 104.15

2 Isopropoxy ethanol

+

OH

OH

OH

OO

CH3

CH3

MW 210.27

Stage 1

STAGE 2 :

+

MW 266.33

Stage 2

OH

OO

CH3

CH3

MW 210.27

Stage 1

ClO

O

OO

CH3

CH3

O

NaOH

MW 92.52

Epichloro hydrine

89

STAGE 3 :

+NH2

CH3

CH3

MW 59.11

Iso Propyl Amine

MW 266.33

Stage 2

O

OO

CH3

CH3

O

1-{4-[2-Isopropoxyethoxy)methyl]phenoxy}

-3-(isopropylamino) propanol bisoprolol

MW 325.44

O NH

OHCH3CH3

OO

CH3 CH3

STAGE 4 :


-3-(isopropylamino) propanol bisoprolol

MW 325.44

O NH

OHCH3CH3

OO

CH3 CH3

Fumeric Acid

MW 441.51

O NH

OHCH3CH3

OO

CH3 CH3 O

OH

O

OH

.

MW 116.07


-3-(isopropylamino) propanol bisoprolol fumarate

90

Mass Balance:


1 4-hydroxy benzyl alcohol 3.75

Final Product 10.00

2 2- Isopropoxy ethanol 3.50


3 Amberlyst-15 1.25



MDC Recycle 19.00



6 Epichlorohydrin 2.88


7 Toluene 27.50

Residue 0.50

8 Sodium borohydride 0.38

Carbon waste 0.63

9 Methanol 31.25

Effluent 46.80

10 Isopropyl amine 2.75

11 MDC 21.25

12 Acetone 40.00

13 Fumaric Acid 3.25

14 Carbon 0.30

15 Water

37.50


17) Brimonidine Tartrate

BRIEF PROCESS:

STAGE 1 : 5-Bromo-N-(4,5-dihydro-1H-imidazol-2-yl) quinoxalin-6-amine brimonidine

• Charged Chorobenzene in Reactor at RT.

• Charge 5-Bromo-6-thiouredo quinoxaline in Chlorobenzene

• Slowly charged a mixture of Chlorobenzene and Ethylene diamine in about mass at RT

• Heat Reaction Mass to 85-90oC. Maintain this temp for 20-22 hrs

• Remove excess of solvent under vacuum.

• Now cool the reaction mass and add Isopropyl alcohol in mass.

91



STAGE 2 : Pure from Crude

• Charged Conc HCl in Reactor at RT.

• Charge 5-Bromo-6-thiouredo quinoxaline Crude in above mass

• Slowly charged Caustic lye in above mass at RT. Stir mass for 1 hrs

• Now cool the reaction mass.



• Wash the Mass with water till pH 6-7

STAGE 3 : Brimonidine Tartrate

• Charged Methanol in Reactor at RT.

• Charge 5-Bromo-6-thiouredo quinoxaline pure and L tartaric acid and carbon in above

mass

• Slowly heat above mass to reflux. Stir mass for 4 hrs at reflux and filter in hot condition

• Now cool the reaction mass. Then chilled the mass



• Dry the material.

Chemical Reaction :


Br

N

NN

S

MW 266.12

Stage 1 Compound

MW 292.13

Stage 1

Br

N

NNH

NH N

NH2

NH2

MW 60.10

Ethylene Diamine

+ + SH2

MW 34.08

STAGE 2 : Purification of STAGE 1

MW 292.13

Stage 1

Br

N

NNH

NH N

M W 292.13

Stage 1

Br

N

NNH

NH N

Crude P ure

92


Tartrate

M W 44 2.2 2

5-B rom o -N-(4,5-d ihy dro-1 H -im ida zol-2-y l)

q uin ox a lin -6 -am ine brim o nidin e ta rtra te

M W 292 .1 3

Sta ge 1

B r

N

NNH

NH N

O HO

O H O

O HOH

M W 1 50.09

L T arta ric Ac id

+

B r

N

NNH

NH N

O HO

O H O

O HOH

.

Mass Balance:


1 Chorobenzene 80.00

Final Product 10.00

2 5-Bromo-6-thiouredo quinoxaline 8.00

Chorobenzene Recycle 77.00

3 Ethylene diamine 5.00

Isopropyl alcohol Recycle 18.00

4 Isopropyl alcohol 20.00


5 Conc HCl 25.00


6 Caustic Lye dilute 40.00

Effluent 106.00

7 Methanol 90.00

Residue 1.00

8 L Tartaric Acid

5.50

Waste Carbon 1.50

9 Carbon

1.00

10 Water

40.00


93

18) Capacitabine

BRIEF PROCESS:

Stage 1

• Charge MDC and 5 Fluoro Cytosine in Reactor.

• Slowly add 5-Methyltetrahydrofuran-2,3,4-triyl triacetate in MDC in RM


• Remove excess of MDC by distillation.

• Use above RM as such in next step.

Stage 2

• Charged step 1 and methanol in Reactor

• Charged n Pentyl chloroformate in above RM and heat the mass.

• Remove excess of Methanol by distillation.

• Charged MDC, water and Conc HCl in above mass and cool the RM.

• Separate both the layer. Wash organic layer with water till pH neutral.



Stage 3

• Charged step 2, Methanol and Caustic lye in Reactor


• Remove excess of Methanol by distillation.

• Charged MDC and water in above mass and cool the RM.


• Give Carbon treatment to above organic layer.

• First cool the organic layer and then chilling is applied.


• Charged Ethyl acetate in reactor.

• Add above wet cake in Ethyl acetate and heat the mass.

• First cool the Filtrate and then chilling is applied.

• Filter the product, wash with chilled n Heptane and dry.

Chemical Reaction:

Stage 1

94

MW 129.09

5 Fluoro Cytosine

F

NH

N

O

NH2

MW 260.24

OCOCH3

O OCOCH3

CH3COO

CH3

5-Methyltetrahydrofuran

-2,3,4-triyl triacetate

+

F

N

N

O

NH2

OCOCH3O

OCOCH3CH3

MW 329.28

Stage 1

Stage 2

F

N

N

O

NH2

OCOCH3O

OCOCH3CH3

MW 329.28

Stage 1

F

N

N

O

NHCOOC5H11

OCOCH3O

OCOCH3CH3

MW 443.42

Stage 2

95

Stage 3

F

N

N

O

NHCOOC5H11

OHO

OHCH3

MW 359.35

Capacitabine

F

N

N

O

NHCOOC5H11

OCOCH3O

OCOCH3CH3

MW 443.42

Stage 2

Mass Balance:


1 5 Fluoro Cytosine

5.00

Final Product 10.00

2 MDC

75.00

MDC Recycle 70.50

3 5-Methyltetrahydrofuran-

2,3,4-triyl triacetate 10.75


4 Methanol

90.00


5 n Pentyl Chloroformate

11.25


6 Conc HCl

8.00

Effluent 60.25

7 Caustic lye

5.00

Carbon 1.00

8 Carbon

0.50

Residue 1.50

9 Ethyl acetate

62.50

10 n Heptane

2.50

11 Water

32.50


96

19) Cinacalcet Hydrochloride

BRIEF PROCESS:

STAGE 1 : Intermediate Stage

• Charged Methanol and 3 Tri fluoro methyl cinnamic acid in Reactor at RT.

• Charged Raney Nickel in above reaction mixture

• Pass Hydrogen gas in above reaction mixture under pressure

• The reaction mixture was heated and stirred and then filter.

• Remove excess of solvent by distillation from filtrate.

• Charge toluene, Boric Acid and Naphthyl ethyl amine in above reaction mixture




STAGE 2 : Cinacalcet Hydrochloride


• Charged Stage 1 and Sodium Borohydride in above reaction mixture


• Remove excess of solvent by distillation from Reaction Mass.

• Charge MDC and Conc HCl in above reaction mixture


• After completion of reaction, charged water in RM and stir it.

• Separate the organic layer and aqueous layer.

• Add carbon in aqueous layer and stir at RT. Filter it by Sparkler.

• Chilled the aqueous layer.

• The separated solid was filtered and dried

Chemical Reaction:

STAGE 1 : Intermediate Stage

97

MW 216.16

3 Trifluoromethyl Cinnamic Acid

MW 171.24

NH2 CH3

+

MW 371.39

Intermediate Stage

O

NHF3C

CH3

O

OHF3C

+OH2

MW 18.01

H2

+

Naphthyl Ethyl Amine

STAGE 2 : Cinacalcet Hydrochloride

MW 393.87

((R)-N-[1-(1-naphthyl)ethyl]-3-[3-(trifluoromethyl)

phenyl]propan-1-amine cinacalcet hydrochloride

NHF3C

CH3

+NaBO2

MW 65.80

NaBH4

MW 371.39

Intermediate Stage

O

NHF3C

CH3

ClH

HCl

98

Mass Balance:


1 Trifluoro methyl Cinnamic acid 7.50


2 Methanol 30.00


3 Raney Nickel 1.30


4 Toluene 15.00

MDC Recycle 5.80

5 Boric Acid 0.30


6 Naphthyl ethyl amine 5.80

Residue 0.50

7 Sodium Borohydride 1.80

Effluent 48.80

8 MDC

7.50

Waste Carbon 1.00

9 Conc HCl

12.50

10 Carbon

0.80

11 Water

30.00


20) Donepezil Hydrochloride

BRIEF PROCESS:

Stage 1

• Charge KSM, Methanol and Palladium Catalyst in Autoclave Reactor

• Heat the reaction mass & maintain it under pressure.

• Release the pressure and filter the mass. Remove Methanol by distillation

• Charged Toluene in filtrate Mass

• Heat the reaction mass & maintain it. Now add water

• Separate both the layers.

• Remove excess of toluene by distillation.

• Use a reaction mass as such for next step

Stage 2

• Charged step 1, IPA and Carbon in Reactor


• Filter the mass by sparker filter

• Charged IPA.HCl in above RM and heat the mass.

99


• Filter the product. And dry it

Chemical Reaction:

STAGE 1 :

MW 377.48

2-[(1-Benzyl-4-piperidyl)methyl]-5,6-dimethoxy

inden-1-one

H3CO

H3CO

N

O

MW 379.49


-2,3-dihydroinden-1-one

H3CO

H3CO

N

O

STAGE 2 :

H3CO

H3CO

N

O

MW 415.96

Donepezil Hydrochloride

H3CO

H3CO

N

O

ClH

MW 379.49


-2,3-dihydroinden-1-one

100

Mass Balance:


1 2-[(1-Benzyl-4-piperidyl)methyl]-

5,6-dimethoxy inden-1-one 10.75

Final Product 10.00

2 Methanol 55.00

Toluene 35.50

3 Palladium Carbon 0.55


4 Toluene 37.50

IPA Recycle 25.00

5 IPA 20.00


6 Carbon 0.25

Effluent 27.30

7 IPA HCl 9.15

Waste Carbon 0.40

8 Water 25.00

Recover Catalyst 0.75

Residue 0.75


21) Gemcitabine Hydrochloride

BRIEF PROCESS:

Stage 1

• Charge Ethyl Acetate and Dibenzoyl Lactum in Reactor.

• Slowly add Sodium bis(2-methoxyethoxy)-aluminumhydride and Tri ethyl amine in RM


• Charged Methane Sulfonyl Chloride in above mass in hot condition

• Remove excess of Ethyl Acetate by distillation.

• Now chilled the reaction mass.

• Filter the reaction mass to separate the solid and dry it.

Stage 2

• Charged Acetyl Cytosine, Toluene and Trimethylsilyl chloride in Reactor


• Charged step 1 in above RM and heat the mass.

• Charged Liq Ammonia in heat and again het the mass.

• Charged water in above mass and cool the RM.


• Add Conc HCl in above mass and heat the reaction mass.

• Separate both layer after cooling the mass.

101



• Charged Acetone and carbon in reactor.

• Add above wet cake in Acetone and heat the mass.

• Filter the mass under hot condition by sparker filter.

• First cool the Filtrate and then chilling is applied.

• Filter the product, wash with chilled acetone and dry.

Chemical Reaction:

STAGE 1 :

M W 376.31

Dibenzoyl Lactum

H 5C 6OCO

O

O

FF

OCOC 6H 5

M W 456.41

S tage 1

H 5C6OCO

O

O

FF

OCOC6H 5

SO

OCH3

STAGE 2 :

102

MW 153.14

Acetyl Cytosine

N

H

N

NH

O

CH3

O

MW 456.41

Stage 1

H5C6OCO

O

O

FF

OCOC6H5

SO

OCH3H

MW 299.51

Silyl Complex

N

H

N

N

OSi(CH3)3

CH3

(H3C)3SiO

+

N

N

NH2

O

OF

F

OH OH

H

ClH

MW 299.66

Gemcitabine Hydrochloride

Mass Balance:


1 Dibenzoyl Lactum

32.50

Final Product 10.00

2 Ethyl Acetate

125.00


3 Sodium bis(2-methoxyethoxy)-

aluminumhydride 17.50


103

4 Tri ethyl amine

5.00


5 Methane Sulfonyl Chloride

32.50


6 Acetyl Cytosine

13.30

Effluent 154.80

7 Trimethylsilyl chloride

2.30

Carbon 0.80

8 Toluene

82.50

Residue 1.80

9 Liq Ammonia 17.50

10 Conc HCl

33.80

11 Acetone

25.00

12 Carbon

0.50

13 Water

15.00


22) Glimepiride

BRIEF PROCESS:

• Charged Acetone, Potassium Carbonate and Sulfonamide derivative in Reactor at RT.

• Charged Trans 4 methyl cyclo hexyl isocyanate in Reaction Mixture.


• Cool the reaction mixture and separate the solid mass by filtration.

• Charged methanol, carbon and above wet cake in Reactor.

• The reaction mixture was heated and stirred then filter by sparkler filter

• Charged Conc HCl in Reaction Mixture.

• Filter the solid mass, wash with water and dry it.

Chemical Reaction:

104

K2CO3

N

CH3

CH3

NH

O O

S

O

NH

O

O

NH

CH3

3-Ethyl-4-methyl-N-[2-(4-{[(trans-4-methylcyclohexyl)carbamoyl]sulfamoyl}

phenyl)ethyl]-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamide glimepiride

MW 490.62

N

CH3CH3

NHO

O SO2NH2+

CH3

OCN

N-{2-[4-(aminosulfonyl)phenyl]ethyl}-3-ethyl-4-

methyl-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamideTrans 4 methyl cyclohexyl isocyanate

MW 351.42 MW 139.19

Mass Balance:



Final Product 10.00

2 Trans Iso Cyanate 6.00


3 Acetone 100.00


4 Potassium Carbonate 7.50


5 Methanol 40.00

Residue 0.80

6 Conc HCl 16.30

Effluent 41.20

7 Carbon 2.50

Carbon 0.50

8 Water 10.00


105

23) Ivabradine

BRIEF PROCESS:

STAGE 1 : (S)-N-{(3, 4-Dimethoxybenzocyclobut-1-yl)}-N-(methyl)]-N-(methyl) amine

Ivabradine Crude

• Charged Potassium carbonate and Acetone in Reactor at RT.

• Charged 3-(3-Iodopropyl)-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one (IDDB) in

above reaction mixture

• Charged Slowly1-[(7S)-3,4-Dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]-N methyl

methanamine hydrochloride (MBC. HCl) in above reaction mixture


• After completion of reaction, Acetone was distilled out to obtain thick slurry

• Charged water and Toluene. Separate both layers.

• Removed Toluene from reaction mass by distillation.

• The obtained syrup subjected for reduction reaction in autoclave by using Palladium on

Carbon in IPA at elevated temperature under hydrogen pressure

• Filter the mass and add Water and Conc HCl in above reaction mass.




STAGE 2 : (S)-N-{(3, 4-Dimethoxybenzocyclobut-1-yl)}-N-(methyl)]-N-(methyl)

amine Ivabradine Pure


• Charged Crude and carbon in above reaction mixture

• The reaction mixture was heated and stirred and filter in hot condition.



Chemical Reaction:

STAGE 1 : (S)-N-{(3, 4-Dimethoxybenzocyclobut-1-yl)}-N-(methyl)]-N-(methyl) amine

Ivabradine Crude

106

MW 466.57

Intermediate Step

NO

OO

I

CH 3CH3

MW 387.21

IDDB

+

OO

NH

CH3

CH3CH 3

.HCl

M W 243.72

M BC.HCl

N

O O

O

CH3

CH 3

O

O

NCH 3

CH3

CH 3

M W 468.59

D BMMA Crude

N

O O

O

CH3

CH3

O

O

NCH3

CH3

CH 3

K2

CO3

H2O HIKCl + ++CO

2+

H2

STAGE 2 : crude to Pure

MW 468.59

DBMMA Crude

N

O O

O

CH3

CH3

O

O

NCH3

CH3

CH3

MW 468.59

DBM MA Pure

N

O O

O

CH3

CH 3

O

O

NCH3

CH3

CH3

107

Mass Balance:




2 Acetone 20.00


3 IDDB 9.00


4 MBC.HCl 6.00


5 Toluene 30.00

Palladium on Carbon Recycle 1.40

6 Palladium on Carbon 0.80


7 IPA 12.00

Effluent 125.60

8 Conc HCl 15.00

Residue 0.40

9 Methanol

60.00

Waste Carbon 1.40

10 Carbon

1.00

11 Water 90.00


24) Nevivolol Hydrochloride

BRIEF PROCESS:

Stage 1

• Charged 6-Fluoro-2-(oxiran-2-yl)-3,4-dihydro-2H-chromene, Benzyl amine, TBAB and IPA

in Reactor.

• Heat to reflux and maintain it for some time.

• Cool RM to RT

• Chilled the RM and filter the product, wash with water and dry it.

Stage 2

• Charged step 1, 6-Fluoro-2-(oxiran-2-yl)-3,4-dihydro-2H-chromene, TBAB and Toluene in

Reactor.



• Distill of excess of solvent.

• Chilled the Reaction and filter it.

• Wash the wet cake by water.

108


Stage 3

• Charged step 2, Palladium on Carbon and Methanol in Autoclave Reactor.

• Heat the reaction mass under hydrogen pressure.

• Stir RM at same temp for several hrs.

• Release the pressure and filter the mass.

• Add carbon in above filtrate and heat it.

• Filter the RM by Sparker filter.

• Pass HCl gas under cooling condition.



• Wash the wet cake by chilled Methanol.


Chemical Reaction:

Stage 1

MW 194.20

+

MW 107.15

Benzyl Amine

O

F

O

6-Fluoro-2-(oxiran-2-yl)-3,4-dihydro

-2H-chromene

NH2

O

F

OH

NH

MW 301.36

Step 1

109

Stage 2

MW 194.20

+

O

F

O

6-Fluoro-2-(oxiran-2-yl)-3,4-dihydro

-2H-chromene

O

F

OH

NH

MW 301.36

Step 1

MW 301.36

Step 2

O

F

OH

O

F

OH

N

CH2Ph

110

Stage 3

MW 441.89

Nebivolol Hydrochloride

O

F

OH

O

F

OH

NH

MW 395.56

Step 2

O

F

OH

O

F

OH

N

CH2Ph

ClH

Mass Balance:


1 6-Fluoro-2-(oxiran-2-yl)-

3,4-dihydro-2H-chromene 10.00

Final Product 10.00

2 Benzyl amine 3.25

IPA 34.50

3 TBAB 1.00

Toluene 28.75

4 Toluene 30.00

Methanol 37.00

5 IPA 37.50


6 Palladium on Carbon 0.25

Effluent 12.00

7 Methanol 40.00

Waste Carbon 0.75

111

8 Carbon 0.50

Spent Catalyst 0.50

9 HCl Gas 1.75

Residue 0.50

10 Water 10.00


25) Pirfenidone

BRIEF PROCESS:

• Charge Di methyl formamide, Bromo benzene and Potassium Carbonate in Reactor.

• Charge Copper Oxide and 5-Methyl-1H-pyridin-2-one in above RM. Heat the mass.

• Remove Di methyl formamide under vacuum.

• After completion of the reaction, extracted the product in Toluene.

• Solvent was removed under vacuum to get crude material

• The solid was treated with aqueous Hydrochloric acid and isolated by adjusting pH to

basic using Sodium Hydroxide to get solid.



Chemical Reaction:

+K

2CO

3

5 Methyl 1 H

Pyrrolin-2-One

MW 109.12

Br

Bromo Benzene

MW 157.01

CH3

NH

O

5-Methyl-1-phenyl

pyridin-2(1H)-one pirfenidone

MW 185.22

CH3

N O

MW 138.21

+ KBr + H2O + CO

2

Mass Balance:


1 Di methyl formamide 22.50

Final Product 10.00

2 Bromo benzene 10.80

Di methyl formamide Recycle 19.80



4 5-Methyl-1H-pyridin-2-one 1.90

Residue 0.80

112

5 Copper Oxide 7.00


6 Toluene 16.00

Effluent 29.70


8 Conc HCl 9.00

9 Water 5.00


26) Sofosbuvir

BRIEF PROCESS:

Stage 1

• Charged Phenyl Phosphorodichloridate, (S)-Isopropyl 2-Amino propanoate hydrochloride,

Potassium carbonate and DMF in Reactor.


• Distilled Excess of DMF under Vacuum.

• Charged Water in above RM under stirring.

• Cool RM to RT

• Chilled the RM and filter the product and dry it.

Stage 2

• Charged step 1, TBAB and Ethyl Acetate in Reactor

• Slow add 1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-ethyltetrahydro-furan-

2-yl)pyrimidine-2,4(1H,3H)-dione in above RM under stirring




• Charged Methanol, wet cake of stage 2 and carbon in reactor.

• Heat the mass and filter in same condition.



• Wash the wet cake by chilled methanol.


113

Chemical Reaction:

Stage 1

M W 210.98

Phenyl

Phosphorodichloridate

MW 167.63

+

(S)-Isopropyl 2-Amino

propanoate hydrochloride

MW 305.67

Step 1

OP

Cl

OCl

CH3

NH2

O

O

CH3 CH3

ClHO

P

Cl

ONH

CH3

O CH3

O

CH3

Stage 2

114

MW 210.98

Phenyl

Phosphorodichloridate

MW 260.22

+

MW 529.45

Sofosbuvir

N

O N

H

O

O

OH

OHCH3F

OP

Cl

ONH

CH3

O CH3

O

CH3

1-[(3R,4R,5R)-3-fluoro-4-hydroxy-

5-(hydroxymethyl)-3-methyltetrahydro

furan-2-yl]pyrimidine-2,4(1H,3H)-dione

OP

ONH

CH3

O CH3

O

CH3

O

O

OH

CH3

FN NH

O

O

Mass Balance:


1 Phenyl Phosphorodichloridate 5.25

Final Product 10.00

2

(S)-Isopropyl 2-

Amino propanoate

hydrochloride

4.50

DMF Recycle

18.75

3 Potassium carbonate 4.25


115

4 DMF 20.00


5 TBAB 0.50



Effluent 28.00

7

1-((2R,3R,4R,5R)-3-fluoro-4-

hydroxy-5-(hydroxymethyl)-

3-ethyltetrahydro-furan-2-yl)

pyrimidine-2,4(1H,3H)-dione

6.25

Waste Carbon

0.75

8 Methanol 25.00

Residue 1.00

9 Carbon 0.50

10 Water 20.00


27) Terbinafine Hydrochloride

BRIEF PROCESS:

Stage 1

• Charged Naphthyl methyl chloride, Methyl amine and toluene in Reactor.


• Charged Water in above RM under stirring.

• Cool RM to RT and separate both layer.

• Cool the Toluene layer.

• Chilled the organic layer and filter the product and dry it.

Stage 2

• Charged step 1, Potassium Carbonate and DMF in Reactor

• Slowly add 1 Chloro 6,6 Dimethylhept-2-en-4-yne in above RM under stirring


• Removed Excess of DMF under vacuum.

• Charged water in above mass.



Stage 3

• Charged step 2 and IPA in Reactor.

• Add carbon in above mass. Stir well and then filter.

• Chilled the RM

• Charged HCl gas slowly in above mass.



116

Chemical Reaction:

Stage 1

MW 176.64

Naphthyl Methylchloride

MW 31.06

+

Methylamine

MW 171.24

Step 1

NH2CH3

Cl NHCH3

Stage 2

MW 156.65

CH3

CH3

CH3

Cl

MW 171.24

Step 1

NHCH3

+

1-chloro-6,6-dimethylhept-2-en-4-yne

N

CH3

CH3

CH3

CH3

MW 291.43

Terbinafine

117

Stage 3

N

CH3

CH3

CH3

CH3

MW 327.89

Terbinafine Hydrochloride

N

CH3

CH3

CH3

CH3

MW 291.43

Terbinafine

ClH

Mass Balance:


1 Naphthyl methyl chloride 6.25

Final Product 10.00

2 Methyl amine 4.00


3 Toluene 30.00

DMF Recycle 34.50

4 1 Chloro 6,6 Dimethylhept

-2-en-4-yne 5.75

IPA Recycle 17.00



6 DMF 37.50

Effluent 67.25

7 IPA 20.00

Waste Carbon 0.75

118

8 HCl gas 2.25

Residue 1.00

9 Carbon 0.50

10 Water 60.00


28) Ursodeoxycholic acid

BRIEF PROCESS:

Step 1

• Charged butanol and 3-hydroxy-7-ketocholanic acid into a reactor.

• The mass was brought to reflux temperature then metallic sodium was added in portions.

• The mass was maintained at reflux for about 30 minutes, and then removed solvent under

vacuum.

• Water and phosphoric acid 85% were subsequently added. The mass was heated to

around 70°C.

• Charged imidazole in to the Reaction mass.

• The suspension was brought at a temperature of 5°-10°C, and then centrifuged and the

solid residue was washed with water.


Step 2

• Charged step 1, butanol and phosphoric acid 85% into a reactor.

• The mixture was heated until complete dissolution. The lower aqueous phase was

separated and eliminated.

• The organic phase was brought to dryness by distillation, and the residue added or

dissolved with methanol and hydrochloric acid.

• The mass was cooled to 0°-5°C, then the suspension was centrifuged and the solid washed

with chilled methanol.


Step 3

• Charged step 2, water and sodium hydroxide were into a reactor.

• The mass was heated at reflux and maintained for 2 hours, and then water was added.

• The solution was brought to 60-65 °C then methanol and Conc HCl were added

• The suspension was stirred at 60°-65°C for at least 15 minutes, then cooled to 20°-25°C

and stirred at this temperature for at least 30 minutes. The suspension was centrifuged

and the solid washed with methanol and water.

• Dry the product to give White to off white solid .

119

Chemical Reaction:

Stage 1

O

OH

O

OH

CH3 H

CH3

H

H

CH3

H

H

3-Hydroxy-7-Ketocholanic Acid

MW 390.56

Ursodeoxycholic Acid Imidazole Salt

MW 461.64

OH

OH

O

OH

CH3 H

CH3

H

H

CH3

H

H

N

NH

Sodium

Phosphoric Acid

Imidazole

Stage 2

OH

O

O

OH

CH3 H

CH3

H

H

CH3

H

H

CH3

MW 406.60

OH

OH

O

OH

CH3 H

CH3

H

H

CH3

H

H

Ursodeoxycholic Acid

MW 392.57

Ursodeoxycholic Acid methyl ester

Phosphoric Acid

Methanol Sodium hydride

Mass Balance:


1 3-hydroxy-7-ketocholanic acid 10.80

Final Product 10.00

2 Butanol 22.50

Butanol Recycle 20.80

3 Sodium metal

1.50


4 Phosphoric acid 85%

9.30

Residue 0.80

5 Imidazole 2.30

Drying loss 6.30

6 Methanol 47.50

Effluent 34.30

120


8 Conc HCl 10.60

9 Water 10.00


GROUP- D :


29) 2 Amino Phenyl Phenyl Sulfide

BRIEF PROCESS:

Step 1 : 2 Nitro Phenyl Phenyl Sulfide

• Charged water in Reactor at RT.

• Charged Caustic Flakes and Thiophenol in Reactor


• Charged 2 Nitro Chloro Benzene in above reaction Mass.




Step 2 : 2 Amino Phenyl Phenyl Sulfide

• Charged Methanol and step 1 in in an autoclave.

• Then add Nickel (Ni) Catalyst in an autoclave.

• Then parching N2 gas in autoclave to removing O2 in autoclave.

• After passed Hydrogen for 4 to 5 hr.

• That time pressure is 2 to 2.5 Kg. Now checked conversion.

• When conversion is completed distill of excess of solvent and then filter the product.


Chemical Reaction :

Step 1 : 2 Nitro Phenyl Phenyl Sulfide

121

MW 231.27

2 Nitro Phenyl Phenyl Sulfide

Water

Caustic Flakes

MW 110.18

Thiophenol

SHNO2

Cl

MW 157.56

2 Nitro chloro benzene

+

+ NaCl + H2O

MW 58.44 MW 18.01

NO2

S

Step 2 : 2 Amino Phenyl Phenyl Sulfide

MW 201.28

2 Amino Phenyl Phenyl Sulfide

Methanol

Raney Nickel, H2 gas

+ 2 H2O

MW 18.01

NH2

S

MW 231.27

2 Nitro Phenyl Phenyl Sulfide

NO2

S

Mass Balance:


1 Thio Phenol 25.60

Final Product 40.00

2 2 Nitro Chloro Benzene 34.40


3 Caustic Flakes 11.20


4 Raney Nickel 0.80

Effluent 57.60

5 Methanol 160.00

6 Water 32.00


122

30) 2-Amino-3,5-dibromobenzaldehyde

BRIEF PROCESS:

Step 1 : 3,5 Dibromo Methyl Anthranilate

• Charged Methanol, Methyl Anthranilate in Reactor at RT. Cool the RM

• Charged Liq. Bromine in above reaction mixture




Step 2 : 3,5 Dibromo Amino Benzylalcohol

• Charged Step 1, THF and Sodium Borohydride in Reactor at RT.


• Remove excess of solvent from RM by Distillation

• Charge Methanol and heat the reaction mass.

• Maintain the reaction mass.

• Distill out excess of Methanol.

• Charge purified water.

• Filter the reaction mass & wash with purified water and collect the wet cake.

• Dry the product

Step 3 : 3,5 Dibromo Amino Benzaldehyde

• Charged Step 2 and Toluene in Reactor at RT.

• Charge Manganese dioxide slowly in above reaction mass


• Filter the reaction mass

• Remove excess of solvent by distillation

• Charged Methanol and heat the RM to clear all mass.

• Chilled the reaction mass.

• The separated solid was filtered wash with methanol and dried

Chemical Reaction :

Step 1 : 3,5 Dibromo Methyl Anthranilate

NH2

COOCH3

MW 151.16

Methyl Anthranilate

+ Br2

MW 159.81

Methanol

Liq. Bromine

NH2

COOCH3Br

Br

MW 308.95

3,5 Dibromo Methyl

Anthranilate

+ HBr

MW 80.91

Hydrobromic Acid

123

Step 2 : 3,5 Dibromo Amino Benzylalcohol

T H F

NH2

CH2OHBr

Br

MW 280.94

3,5 Dibromo Amino

Benzylalcohol

NH2

COOCH3Br

Br

MW 308.95

3,5 Dibromo Methyl

Anthranilate

Sodium

Borohydride

Step 3: 3,5 Dibromo Amino Benzaldehyde

NH2

CHOBr

Br

MW 278.93

3,5 Dibromo Amino

Benzaldehyde

Manganes

Dioxide

NH2

CH2OHBr

Br

MW 280.94

3,5 Dibromo Amino

Benzylalcohol

Toluene

Mass Balance:


1 Methyl Anthranilate 24.00

Final Product 40.00

2 Methanol 216.00

Methanol Recovery 189.60

3 Bromine 25.60

THF Recovery 59.20

4 THF 68.00

Toluene Recovery 92.00

5 Sodium Borohydride 4.80

Drying + Distillation Loss 49.20

6 Toluene 96.00

Residue 2.80

7 Manganese dioxide 23.20

Effluent 136.80

8 Water 112.00


124

31) Dibenzo [b, f][1,4]Thiazepin-11(10H)-One

BRIEF PROCESS:

• Charged 2 Amino phenyl phenyl sulfide and Ethyl chloro formate in Reactor at RT


• Charged PPA and water in above reaction mass.

• Heat the RM and stir well for several time.

• Separate Organic layer and aqueous layer.

• Charged water in above organic layer and heat under stirring.



Chemical Reaction :

MW 227.28

Ethyl Chloro Formate

MW 108.52

PPA

+ HCl

MW 36.46

MW 201.28

2 Amino Phenyl Phenyl Sulfide

NH2

S

N

H

S

O

Dibenzo[b,f][1,4]Thiazepin-11(10H)-One

+

MW 46.09

C2H5OH

Mass Balance:


1 2 Amino phenyl phenyl sulfide 38.00

Final Product 40.00

2 Poly Phosphoric Acid PPA 120.00

Drying Loss 13.20

3 Ethyl Chloro formate 25.20

Effluent 270.00

4 Water 140.00


32) 4 Methyl Acetophenone

BRIEF PROCESS:

• Charge Acetyl chloride in Glass Lined reactor.

• Charge AlCl3 by maintaining the temperature less than 10oC during 2-3 hrs.

• Cool above suspension to 0oC to 5

oC

125

• Charged toluene slowly by maintaining temperature 0oC to 5

oC in about 5 hrs

• After completion of addition, stir the reaction mixture at 10oC to 15

oC

• In Quencher, take chilled water and Conc HCl

• Reaction mixture was added to mixture of HCl and water by maintaining temperature less

than 50oC

• Separate the organic layer

• Organic layer was concentrated under reduce pressure

• Distilled finished product under high Vacuum.

Chemical Reaction :

MW 92.14

CH3

Toluene

MW 78.50

+ HCl+

MW 36.46

Hydrochloric Acid

CH3COCl

Acetyl Chloride

COCH3

CH3

MW 134.18

4 Methyl

Acetophenone

Aluminium

Chloride

Mass Balance:


1 Acetyl Chloride 26.00

Final Product 40.00

2 Toluene 48.00


3 Aluminum Chloride 64.00


4 Conc HCl 28.00

Residue 1.60

5 Water 96.00

Effluent 188.00


33) 2-Chloro-1,3-bis(dimentylamino)trimethinium hexafluorophosphate

BRIEF PROCESS:

Hexa Fluoro Phosphoric Acid

• Charge Poly phosphoric acid in reactor. Chilled the PPA under stirring.

• Charged slowly HF Gas in above RM under vigorous stirring.

• RM is then warmed to give a clear solution of final product

126

2-Chloro-1,3-bis(dimentylamino)trimethinium hexafluorophosphate

• Charge Dimethylformamide, Chloroacetyl chloride and in above GLR.

• Charge Phosphorus Oxychloride) in above RM.

• RM is then heated to give a clear yellow solution

• After completion of the addition, the reaction mixture is cooled.

• Charged chilled Caustic solution and hexafluorophosphoric acid solution in water in RM

• The RM is maintained at same temp for 2 hr, then the solids are collected by Centrifuged.

• The crude solids are washed with water

• The light-yellow solids are collected by filtration, washed with cold water

• Dry the product to give 2-chloro-1,3-bis(dimethylamino) trimethinium

hexafluorophosphate as a light-yellow solid.

Chemical Reaction:

Polyphosporic Acid

MW 98.00

Hydrofluoric Gas

MW 20.00

H3PO4 + 6 HF H6F6.H3PO4

Hexa Fluoro Phosporic

Acid

MW 218.00

+

POCl3

NaOH

HFP

CH3

O

N H

CH3

Dimethyl Formamide

MW 93.09

N

ClCH3

CH3

N+

CH3

CH3PF6

-

2-Chloro-1,3-bis(dimethylamino)

triethinium hexafluoro phosphate Salt

MW 306.62

Cl

O

Cl

Chloro Acetyl Chloride

MW 112.94

Mass Balance:


1 Di methyl formamide 14.40

Final Product 40.00

2 Chloro acetyl chloride 16.00

Drying loss 10.40

3 Phosphorus Oxychloride 22.00

Effluent 97.60


5 Hexafluoro phosphoric acid 36.00

6 Water 33.20


127

34) 2,3-Dibenzoyl-D-Tartaric acid (DBDT)

BRIEF PROCESS:

• Charge benzoyl chloride in GLR at RT.

• Charge D-(-)-tartaric acid in RM at RT.

• Heat Reaction Mass. Maintain this temp for 3 to 4 hrs.

• Charge Toluene in Reactor. Heat to reflux for 30 min.

• Cool RM to RT.

• Filter the RM and wash with Chilled toluene.


Chemical Reaction :

+

Toluene

O

OH

OHO

OH

OH

D Tartaric Acid

MW 150.09

O Cl

Benzoyl Chloride

MW 127.55

2,3 Dibenzoyl D Tartaric Acid

MW 302.28

O

O

OHO

O

OH

+ HCl

Mass Balance:


1 Benzoyl Chloride 35.60

Final Product 40.00

2 D Tartaric Acid 21.20


3 Toluene 60.00


Residue 0.80


35) Ethyl Trifluoro Acetate

BRIEF PROCESS:

• Charged Ethanol, Trifluoro acetic acid and Sulfuric acid in Reactor at RT.

• Applied heating to reaction mass

• Maintaining Reaction Mass to 65-68°C for 4.00 hrs

• Cooling Reaction Mass to 45-50°C

• Add water and stir for 15 min. Separate Organic Layer

• Add Sodium Carbonate Solution (5%) in above Organic Layer and stir for 15

min. Separate Organic Layer

• Distill Organic Layer for purified Product.

128

Chemical Reaction :

FO

OH

F

F

MW 114.02

Trifluoro Acetic Acid

FO

O

F

F

CH3

MW 142.08

Ethyl Trifluoro Acetate

Ethanol

Sulfuric Acid

Sodium Carbonate

Water

Mass Balance:


1 Trifluoro Acetic Acid 34.40

Final Product 40.00

2 Ethanol 20.00

Distillation Loss 4.80


Residue 1.20

4 Sulfuric Acid 4.80

Effluent 34.80

5 Water 20.00


36) m Phenoxy benzyl alcohol

BRIEF PROCESS:

• Take m Phenoxy Benzaldehyde in an autoclave.





• When conversion is completed than filter of m Phenoxy Benzyl alcohol.

Chemical Reaction :

MW 198.21

m Phenoxy Benzaldehyde

CHOO

Hydrogen Gas

Nickel Catalyst

MW 200.23

CH2OHO

m Phenoxy Benzyl Alcohol

129

Mass Balance:


1 m Phenoxy Benzaldehyde 39.92

Final Product 40.00

2 Nickel Catalyst 0.56

Filter Loss 0.04

Nickel Catalyst Regenerated 0.44


37) P Methoxy Phenyl Acetonitrile

BRIEF PROCESS:

Step 1 : p Anisic Alcohol

• Take 4 Methoxy Benzaldehyde in an autoclave.





• When conversion is completed than filter of 4 Methoxy Benzyl Alcohol.

Step 2 : p Methoxy Benzyl chloride

• Charged Conc. HCl in reactor.

• Then Charged Para Anisic Alcohol in above RM in 2 to 3 hours.

• After Addition, Maintain for 6 hours at same temp.

• Now Charged Toluene in RM and then cool to room temp.

• After settling, separate layers.

• Wash toluene layer with water

• Use Toluene layer for next step.

Step 3 : p Methoxy Phenyl Acetonitrile

• Take water in reactor and dissolve Sodium Cyanide and TBAB.

• After charged Step-02 in above RM maintain it 70 ~ 75oC.

• Then maintain same temp. for 6-7 hrs.

• Cool to room temp, Separate layers.

• Collect upper organic layer.

• Wash the Organic layer by sodium chloride solution.

• Water wash in to the organic layer & separated the organic layer.

• Collect organic layer, distil off toluene completely.

• Now distill the organic layer then collect finished P-Methoxy Phenyl Acetonitrile.

130

Chemical Reaction :

Step 1 : p Anisic Alcohol

MW 136.15

p Anisic Aldehyde

Hydrogen Gas

Nickel Catalyst

CHO

OCH3

MW 138.16

p Anisic Alcohol

CH2OH

OCH3

Step 2 : p Methoxy Benzyl chloride

Conc HCl

MW 156.61

p Methxoy Benzyl chloride

CH2Cl

OCH3

MW 138.16

p Anisic Alcohol

CH2OH

OCH3

Step 3 : p Methoxy Phenyl Acetonitrile

NaCN

MW 147.17

p Methxoy Phenyl Acetonitrile

CH2CN

OCH3

MW 156.61

p Methxoy Benzyl chloride

CH2Cl

OCH3

Mass Balance:


1 4 Methoxy Benzaldehyde 41.60

Final Product 40.00

2 Nickel Catalyst 12.80


3 Conc HCl 96.00

Nickel Catalyst Regenerated 1.20

131

4 Toluene 80.00

Distillation Loss 4.00

5 Sodium Cyanide 14.40

Effluent 194.00

6 Sodium Chloride 4.80

7 Water

64.00


38) Phthaloyl Amlodipine

BRIEF PROCESS:

• Take Ethyl-4-(2-phthalimido) ethoxy acetoacetate, o Chloro Benzaldehyde and Acetic

Acid in Reactor.

• Then add Methyl 3 Amino Crotonate in above reaction mass.

• Then Heat the mass with continues stirring.

• Add water in above mass and stir at same temp.

• Cool the reaction mass.

• The separated solid was filtered, wash with water and dried.

• Charged Methanol and above dry material in a reactor.


• Cool the mass and filter the product. Dry it.

Chemical Reaction :

132

Methyl 3 Amino Crotonate

Acetic Acid

MW 319.31

Ethyl-4-(2-phthalimido) ethoxy acetoacetate

MW 138.16

o Chloro Benzaldehyde

CHO

ClN

O

O

OO

O O

CH3 +

N

O

O

ON

H

Cl

CH3

COOCH3H5C2OOC

MW 538.98

Phthaloyl Amlodipine

Mass Balance:


1 Ethyl-4-(2-phthalimido)

Ethoxy acetoacetate 28.00

Final Product 40.00

2 O Chloro Benzaldehyde 13.20


3 Acetic Acid 4.00

Residue 1.20

4 Methyl 3 Amino Crotonate 11.20

Drying + Distillation Loss 13.60

133

5 Methanol 120.00

Effluent 43.20

6 Water 40.00


39) Sulfanilamide

BRIEF PROCESS:

Step 1 :

• Charged slowly Chloro Sulfonic Acid in Reactor at RT and Cool it

• Charged Acetanilide in Reactor

• The reaction mixture was slowly heated and stirred well.



• Quench the reaction mass in chilled water.

• The separated solid was filtered.

• Charged Ammonia Solution in Reactor and Chilled it.

• Add above vet cake slowly with maintaining temp.

• Raise the temp of RM to RT.

• The separated solid was filtered and use as such in next step

Step 2 :

• Charged Conc HCl and water in Reactor at RT

• Charged Step 1 in Reactor

• The reaction mixture was slowly heated and stirred well.



• Add Soda Ash Solution in above RM.

• The separated solid was filtered, wash with water and dried.

Chemical Reaction :

Step 1 :

Chloro Sulfonic Acid

NHCOCH3

MW 135.16

Acetanilide

NHCOCH3

SO2Cl

MW 214.24

Step 1

Ammonia Solution

NHCOCH3

SO2NH2

134

Step 2 :

MW 172.20

Sulfanilamide

Conc HCl

NH2

SO2NH2

MW 214.24

Step 1

NHCOCH3

SO2NH2

Soda Ash

Mass Balance:


1 Acetanilide 36.00

Final Product 40.00

2 Chloro Sulfonic Acid 62.40

Drying + Evaporation

Loss 18.40

3 Ammonia Solution 116.00

Effluent 338.40

4 Conc. HCl 48.00

5 Soda Ash 22.40

6 Water 112.00


40) 3-Trifluoromethyl Cinnamic Acid

BRIEF PROCESS:

• Charged Hydrochloric acid, Water and 3 Trifluoromethyl Aniline in Reactor at RT.

• Charged aqueous Sodium Nitrite in above reaction mixture at RT

• Charged slowly Acrylonitrile in above reaction mixture.

• Add Caustic flakes and water in above reaction mass.

• The reaction mixture was heated and stirred. Now cool the reaction mass.

• Dilute Sulfuric Acid was added to the reaction mixture



Chemical Reaction :

135

M W 208.57

Interm ed iate Step

NH2

F 3C

M W 161.12

3 Trifluo ro m eth yl Aniline

N aNO2+ + 2 HC l

M W 68.99M W 36.46

2 H 2O+ + NaCl

M W 18.02

M W 58.44

N+

N

F3C

Cl-

M W 216.16

3 Trifluoro m ethyl C in nam ic Acid

+

O OH

F 3C

+

M W 53.06

H 2O

M W 18.02

+

N aCl

M W 58.44

N2 +

M W 28.01

CH2 CN

NaO H

M W 39.99

+

+NH3

M W 17.03

Mass Balance:


1 3 Trifluoromethyl Aniline 32.00


2 Conc HCl 53.20

Drying Loss 10.00

3 Sodium Nitrite 16.00

Effluent 126.80

4 Acrylonitrile 11.60


6 Conc Sulfuric Acid 14.00

7 Water 40.00


GROUP- E :


41) Glipizide

BRIEF PROCESS:

• Charged Acetone, Potassium Carbonate and Sulfonamide derivative in Reactor at RT.

• Charged Cyclo hexyl isocyanate in Reaction Mixture.

136


• Cool the reaction mixture.

• Filter the wet cake.

• Charged Wet cake and Methanol in Reactor. Heat the mass with stirring.

• Cool the reaction mixture.

• Filter the wet cake.

• Charged Activated Carbon in Filtrate.

• Filter the reaction mass by sparker filter.

• Charged Conc HCl in Filtrate.

• Filter the solid mass, wash with water and dry it

Chemical Reaction :

K2CO3

+

NCO

Cyclohexyl isocyanate

MW 320.37 MW 125.16

MW 445.53

Glipizide

NH

S

O

ONH2

ON

NCH3

5-Methyl-N-[2-(4-sulfamoylphenyl)ethyl]

pyrazine-2-carboxamide

NH

S

O

ONH

ON

NCH3

O

NH

Mass Balance:



Final Product 10.00

2 Cyclo Hexyl Iso Cyanate 3.50


137



4 Acetone 80.00


5 Methanol 60.00

Residue 0.25

6 Carbon 0.25

Waste Carbon 0.50

7 Conc HCl 16.00

Effluent 106.00

8 Water 85.00


42) Modafinil

BRIEF PROCESS:

• Charge Acetic Acid and 2-[(Diphenylmethyl)sulfanyl]acetamide in reactor at RT.

• Heat the Reaction Mass upto 50oC.

• Charged Slowly Hydrogen Peroxide in above reaction mass at same temp.

• Charged water under stirring and cool the reaction mass.

• Filter the solid product, wash with water and dry it.

• Charged Methanol and above product in reactor.

• Heat the mass upto reflux

• Remove excess of solvent by filtration.

• Charged water in reaction mass and heat it.


• Charged Methanol and above product in reactor.

Chemical Reaction :

M odafilin

M W 273.35M W 257.35

S

N H2

O

2-[(Diph enylm ethy l)sulfany l]acetam ide

S

NH 2

OO

Mass Balance:


1 2-[(Diphenylmethyl)sulfanyl]

acetamide 12.00

Final Product 10.00

2 Acetic Acid

16.25


138

3 Hydrogen Peroxide

6.75


4 Methanol

37.50

Effluent 73.00

5 Water

50.00


43) Mycophenolate Mofetil

BRIEF PROCESS:

• Charge Ethanol, PTSA, 2 Morpholinoethanol and Mycophenolic acid in reactor at RT.

• Heat the Reaction Mass upto Reflux.

• Distillation out excess of solvent from reaction mass.



Chemical Reaction :

M W 131.17M W 320.34

Mycophenolic acid

O

O

CH 3

OCH 3

OH

OH

O

CH 3OH

N

O

+

O

O

CH 3

OC H 3

OH

O

O

CH 3 N

O

M W 433.49

M ycophenolate Mofetil

2 Morpholino ethanol

Mass Balance:


1 Mycophenolic acid 7.63

Final Product 10.00

2 2 Morpholino ethanol

5.74

Ethanol Recycle 35.25

139

3 PTSA

0.38


4 Ethanol

37.50

Effluent 32.75

5 Water

30.00


44) Tadalafil

BRIEF PROCESS:

• Charge Methanol, Methyl amine and Methyl 1-(1,3-benzodioxol-5-yl)-2-

(chloroacetyl)-2,3,4,9-tetrahydro-1H-b-carboline-3-carboxylate in reactor at RT.

• Heat the Reaction Mass upto 65oC.

• Distill off excess of Methanol



Chemical Reaction :

MW 426.85

N

NH

O

O

O

Cl

H3CO O

Methyl 1-(1,3-benzodioxol-5-yl)-2-(chloroacetyl)

-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate

MW 389.40

N

NH

O

O

N

O

O

CH3

Tadalafil

Mass Balance:


1 Carboxylate Intermediate 11.38

Final Product 10.00

2 Methanol

50.00


3 Methyl Amine

14.75


4 Water

80.00

Effluent 94.63


140

45) Tranexamic Acid

BRIEF PROCESS:

STAGE-1:

• Charge Methanol, Sodium Methoxide and Benzoate derivative in Autoclave.

• Charged Ruthenium Catalyst and Hydrogen gas in above reaction mass.

• Heat the reaction mass under stirring. Cool the RM.

• Filter the catalyst.

• Distill off excess of solvent.

• Use this reaction mass as such in next step.

STAGE-2:

• Charge Methanol, Potassium hydroxide and step 1 in reactor.

• Heat the reaction mass under stirring. Now add Carbon it reaction mass.

• Charged Ruthenium Catalyst and Hydrogen gas in above reaction mass.

• Heat the reaction mass under stirring. Cool the RM.

• Filter the mass.

• Charged Conc HCl in above filtrate under stirring.

• Chilled the reaction mass and separate solid mass.

• Wash the solid mass with water till pH neutral.


Chemical Reaction :

STAGE-1:

M W 207.23

N H

C O O C H 3

O

C H 3

M W 213.27

S tep 1

N H

C O O C H 3

O

C H 3

M ethyl 4-[(a cetylam ino )m eth yl] ben zoa te

STAGE-2:

MW 157.21

Tranexamic Acid

NH2

COOH

MW 213.27

Step 1

NH

COOCH3

O

CH3

141

Mass Balance:


1 Benzoate Derivative 14.50

Final Product 10.00

2 Sodium Methoxide

4.13


3 Methanol

45.00


4 Ruthenium

0.25

Waste Carbon 0.63

5 Hydrogen gas 7500 M3

Residue 0.50

6 Nitrogen 750 M3

Effluent 58.50

7 Potassium hydroxide

5.25

8 Conc HCl

16.25

9 Carbon

0.50

10 Water

30.00


46) 5-(1-Carboxyethyl)-2-Phenylthio-Phenylacetic Acid

BRIEF PROCESS:

• Charged Toluene and 2 Phenylthio 5 Propionyl Phenyl Acetic Acid in Reactor

• Charged Triethyl Formate slowly in above RM under stirring.

• Heat the reaction mixture and add slowly Zinc Dust in it.

• The reaction mixture was heated and stirred at reflux temp for several hrs.

• Charged Bromine slowly in above reaction mass with maintaining temp around 80oC.

• Add Activated carbon in it and stir for some time as same temp.

• Filter the RM in hot condition by sparker.

• Wash filtrate by water.

• The filtrate was cooled and then chilled


142

Chemical Reaction :

MW 316.37

CH2COOH

S

CH3

HOOC

Zn/Bromine

MW 300.37

2 Phenylthio 5 Propionyl Phenyl Acetic Acid

CH2COOH

S

O

CH3

Methanol/Toluene

5-(1-Carboxyethyl)-2-Phenylthio-phenylacetic Acid

Mass Balance:


1 2 Phenylthio 5 Propionyl

Phenyl Acetic Acid 10.70

Final Product 10.00

2 Toluene 40.00

Toluene (Recovery) 37.30

3 TriethylFormate 7.70


4 Zinc Dust 1.00

Residue 0.80

5 Bromine 7.50

Waste Carbon 0.50

6 Carbon 0.30

Effluent 16.50

7 Water 6.70


143

47) Zaltoprofen

BRIEF PROCESS:

• Charged Poly Phosphoric Acid and 5(1-Carboxyethyl)-2-Phenylthio-phenylacetic Acid

in Reactor

• Heat the reaction mixture and add slowly water in it.

• The reaction mixture was heated and stirred at reflux temp for several hrs.

• Cool the RM and charged EDC slowly in above reaction mass with maintaining temp

around 70oC.

• Separate both layer. Wash EDC layer by water.

• Add Activated carbon in EDC layer and stir for some time as same temp.

• Filter the RM in hot condition by sparker.

• The filtrate was cooled and then chilled


Chemical Reaction :

MW 298.35

Zaltoprofen

PPA/EDC

MW 316.37

5-(1-Carboxyethyl)-2-Phenylthio-phenylacetic Acid

CH2COOH

S

CH3

HOOC

CH3

HOOC

S

O

144

Mass Balance:


1

5(1-Carboxyethyl)-2-

Phenylthio-

phenylacetic Acid

11.67

Final Product

10.00

2 Poly Phosphoric Acid 30.00

EDC (Recycle) 21.67

3 EDC 23.33


4 Carbon 0.67

Residue 0.83

5 Water 50.00

Waste Carbon 1.00

Effluent 79.17


145

ANNEXURE - IV

WATER CONSUMPTION AND WASTEWATER GENERATION

WATER CONSUMPTION

SR.

No.

WATER

CONSUMPTION

QUANTITY (KL/DAY)

Existing Additional Total after proposed

expansion

1. Domestic 2.6 10 12.6

2. Process 2.55 24.4 26.95

3. Boiler 2.0 30 32.0

4. Cooling 2.0 40 42.0

5. Washing 0.1 10 10.1

6. APCM- Scrubber - 10 10

7. Other - 10 10

8. Gardening - 20 20

TOTAL (Industrial) 6.65 124.4 131.05

TOTAL (Domestic +Industrial) 9.25 154.4 163.65

WASTE WATER GENERATION

SR.

No.

WASTE WATER GENERATION

QUANTITY (KL/DAY)

Existing Additional Total after proposed

expansion

1. Domestic 2.6 10 12.6

2. Process 2.55 43 45.55

3. Boiler 0.225 3 3.225

4. Cooling 0.225 4 4.225

5. Washing 0.1 10 10.1

6. APCM- Scrubber - 10 10

7. Other - 6 6

8. Gardening -- -- --

TOTAL (Industrial) 3.1 76 79.1

TOTAL (Domestic +Industrial) 5.7 86 91.7

146

Water Balance Diagram (Existing):

(Unit-KL/Day)

Water – 9.25 KL/Day

Domestic- 2.6 Industrial – 6.65

2.6 KL/Day �

Specific

tank/soak pit

system Process- 2.55 Washing- 0.1 Boiler- 2.0

Cooling- 2.0

Process- 2.55 Washing- 0.1 Boiler- 0.225 Cooling- 0.225

ETP CETP (EICL)-3.1 KLD for

further treatment

147

Water Balance Diagram (TOTAL AFTER PROPSED EXPANSION ):

(Unit: KL/Day)

Fresh Raw Water [Bore well] 101.96 KL/Day

Domestic 12.6 KL/Day

Industrial 131.05 KL/Day

Gardening 20 KL/Day

Process: 26.95 KL/Day

Cooling 42 KL/Day

Septic tank/ Soak Pit

45.55 KL/Day

Total = 79.1 KL/Day [High COD & TDS 20 kl/day + Low COD/TDS 59.1 KL/day]

4.225 KL/Day

16.41 KL/day CETP: NIA for further

treatment

Washing 10.1 KL/Day

10.1 KL/Day

Boiler 32 KL/Day

3.225 KL/Day

APCM- 10 KL/Day

10.0 KL/Day

Condensate 19 KL/day Reuse in

C.T.

RO

High COD & TDS 20 kl/day Stripper / MEE

Low COD/TDS 59.1 KLl/day ETP

Others 10 KL/Day

6.0 KL/Day

Reuse 42.69 KL/day In cooling /Boiler/APCM

Re-sue of Water 61.69 KL/Day

148

ANNEXURE - V

EFFLUENT TREATMENT PLANT

EXISTING :

PROCESS DESCRIPTION: ETP (EFFLUENT TREATMENT PLANT)

The streams generating high Ammonical nitrogen will be segregated from the process

stream and will be treated with sulphuric acid to give ammonium sulfate. The solution will

be then taken to the distillation kettle wherein it will be evaporated till salt is formed. The

salt will be sent to NECL, along with the process sludge.

The characteristics of composite untreated effluent sample were found to be:

Sr. Parameter Results

(mg/Lit)

1. pH 2.4

2. Suspended Solids 742

3. TDS 48260

4. COD 10500

5. BOD 826

6. NH3N 1378

7. BOD:COD 0.078

It was observed that the composite effluent is acidic with high concentration of Ammonical

nitrogen. Hence, NaOH is added to raise the pH to10. The mixture is then stirred for two

hours, after which the pH reduces to 7.6.This reduces the Ammonical nitrogen to 184

mg/Lit. The sludge settled at bottom is removed and taken to sludge drying bed. After the

NaOH treatment, the neutralized effluent is taken to the primary treatment tank wherein

the coagulation and flocculation process is carried out with the help of hydrated lime and

alum. Chlorination will also be carried out if required to reduce the Ammonical nitrogen and

the COD. This is carried out for an hour, after which the effluent is taken to the primary

settling tank wherein the separation of the treated effluent and the sludge takes place. The

sludge is then transferred to the sludge drying bed and the supernatant to the final

collection tank.

Effluent Treatment Plant (Dimension):

S.N. Name of unit Size

1 Collection Cum Holding

Tank 20 KL

2 Neutralization Tank 20 KL

3 Primary

(chemical)Treatment Tank 20 KL

149

4 Holding Tank 40 KL

5 Filter Press 18” size

6 Dried sludge storage Tank 225 Sq.Ft.

7 Hy. Lime Solution Dosing 200 Lit.

8 Alum Solution Dosing 200 Lit.

9 NaOH Solution Dosing 200 Lit.

Flow Diagram:

150

The characteristic of treated effluent sample was found to be:

Sr.

No. Parameter

Results

(mg/L)

1. pH 7.4

2. COD 1450

3. BOD3 110

4. NH3N 32

Proposed :

PROCESS DESCRIPTION: ETP (EFFLUENT TREATMENT PLANT)

1.0 Design Basis

1.1. Design flow

Stream I = 59.1 m3/day

Stream II = 20 m3/day

1.2 Untreated Effluent Characteristics of Stream I

Sr.No. Parameters Value

1. pH = 4.0-9.0

2. Total Dissolved Solids < 2000 mg/L

3. Suspended Solids < 1500 mg/L

4. BOD3 < 3500 mg/L

5. COD < 8000 mg/L

6. O & G < 100 mg/L

1.3 Treated Water Characteristics


1. pH = 6.5 – 7.5

2. Total Dissolved Solids < 2000 mg/L


4. BOD3 < 400 mg/L

5. COD < 1500 mg/L

6. O & G < 10 mg/L

151

Untreated Effluent Characteristics (High COD & TDS)


1. pH = 5.0-7.0

2. Total Dissolved Solids < 1,50,000 mg/L


4. COD < 25000 mg/L

5. BOD3 < 6000 mg/L

2.0 TREATMENT PHILOSOPHY:

Stream I (59.1 KLD)

First all non-toxic and biodegradable low TDS streams of wastewater shall pass through Oil

& Grease Removal Tank (OGRT) where floating oil and grease shall be removed manually

from the wastewater and collected in Oil & Grease Collection Tank (OGCT-01). Then effluent

shall be collected in Equalization cum Neutralization Tanks (ENTs). where the continuous

addition and stirring of caustic solution is done to maintain neutral pH of wastewater from

Caustic Dosing Tanks (CDT-01) as per requirement by gravity. Pipe grid is provided at bottom

of the ENTs to keep all suspended solids in suspension and to provide proper mixing. 2 nos.

of Air Blowers (1 stand-by) shall supply air to pipe grid.

Then after, equalized wastewater shall be pumped to Flash Mixer. Here, Alum and

Polyelectrolyte shall be dosed from Alum Dosing Tank (ADT-01) and Polyelectrolyte Dosing

Tank (PEDT-01) respectively by gravity into FM-01 to carry out coagulation by using a Flash

Mixer. Then after, coagulated wastewater shall be settled in Primary Tube Settler (PTS-01).

Clear supernatant from PTS-01 shall be passed in Aeration Tank (AT-01). Here,

biodegradation of organic matter of the wastewater shall be carried out by bacteria

(suspended growth) in the AT-01 and for that oxygen shall be supplied by 2 nos. of air

blowers (B-02) through diffusers. Air blowers also keep MLSS in suspension. Nutrient shall

be added from Nutrient Dosing Tank (NDT-01) as per requirement.

Then after, wastewater shall go to Secondary Settling Tank (SST-01) from AT-01. Here, the

suspended solids shall be settled. Sludge shall be removed from bottom of SST-01 and

pumped to AT-01 to maintain MLSS and excess activated sludge shall be sent to Sludge

Drying Beds (SDBs-A/B).

Clear effluent from SST-01 shall be collected in of Intermediate Sump (IS-01) by gravity. In IS

,B-01 supply air in air grid to keep solid in suspension, Then after, the wastewater shall be

pumped through Dual Media Filter (DMF-01) to remove left out TSS and polishing treatment

and then collected in Treated Effluent Sump (TES-01).Then it will sent to RO Unit for further

treatment. RO treated water shall be reuse in Boiler and cooling in Plant and reject shall be

sent to CETP (M/s NIA) for further treatment.

152

Sludge settled in PTS-01 and excess sludge from SST-01 shall be collected in sludge Drying

Beds (SDBs-A/B) where, drying shall be carried out before storage in HWSA and ultimate

disposal to TSDF. Filtrate from SDBs-A/B and backwash from DMF shall be collected in ENTs-

01 for further treatment.

Stream II (20 KLD)

High TDS stream from plant shall be collected in Collection Tank before sent to common

Multistage Effect Evaporator Plant for further treatment plant.

Size of Tanks for proposed ETP

Sr.

No. Name of Unit Tag No.

Size in Meters

(L X B X (LD+FB) Nos. MOC

For Low TDS Streams (59.1 KLD)

Inlet Units

1. O & G Removal Tank OGRT-

01

3.5 x 1.0 x (1.2+0.5) 1

RCC M25 with

Epoxy Lining

2. O & G Collection Tank OGCT-

01 1.0 x 0.75 x (0.9+ 0.8) 1

RCC M25 with

Epoxy Lining

3. Equalization cum

Neutralization Tanks ENTs-01 3.5 x 3.0 x (3.0 +0.7) 2

RCC M25 with

Epoxy Lining

4. Caustic Dosing Tank CDT-01 1000 Lit 1 HDPE

Primary Treatment

5. Flash Mixer FM-01 1.0x 1.0 x (2.5+0.3) 1 RCC M25

6. Primary Tube Settler

PTS-01 3.0 x 2.0 x (2.0

+0.75HB +0.5) 1 RCC M25

7. Alum Dosing Tank ADT-01 1000 Lit 1 HDPE

8. Poly Dosing Tank PDT-01 750 Lit 1 HDPE

Secondary Treatment

9. Aeration Tank AT-01 9.0 x 5.0 x (4.5 +0.5) 1 RCC M25

10. Secondary Settling

Tank SST-01

3.5 x 2.0 x (2.5

+0.75HB+0.5) 1 RCC M25

11. Nutrient Dosing Tank NDT-01 750 Lit 1 HDPE

Tertiary + Advance+sludge dewatering Treatment

12. Intermediate Sump IT-01 2.0 x 2.0 x (3.0+0.5) 1 RCC M25

13. Dual Media filter DMF-01 3 m3/hr 1 FRP

14. Treated Effluent

Sump TES-01 5.0 x 4.0 x (3+0.5) 1 RCC M25

15. RO Unit RO-01 59.1 KLD 1 PVDF+SS

16. Sludge Drying Beds SDBs-01

4.0 x 3.0 3

Brk. Masonry

+ PCC Bedding

For High TDS Stream (20 KLD)

17. Collection tank CT-01 4.0 x 3.5 x (3+0.5) 1 RCC M25

153

FLOW DIAGRAM:

154

ANNEXURE-VI

DETAILS OF HAZARDOUS WASTE GENERATION & DISPOSAL

CAT.

NO.

HAZARDOUS

WASTE

Existing

Quantity Additional

Quantity

Total

Quantity METHOD OF DISPOSAL

5.1 Used Oil 5

Lit/Month

15

Lit/Month

20

Lit/Month

Collection, Storage,

Transportation and

Disposal by seeling to

registered re-refiners

28.3 Spent Carbon 0.045

MT/Month

6.78

MT/Month

6.825

MT/Month


Transportation and sent

to cement industries for

co-processing or

incineration at CHWIF.

35.3 ETP Sludge 1.24

MT/Month

8.76

MT/Month

10.0

MT/Month


Transportation and

Disposal at TSDF site of

NECL Nandesari.

33.1 Discarded

Bags/

Containers/

barrels/

Liners

100

Nos./Month

150

Nos./Month

600

Nos./Month

800

Nos./Month

700

Nos./Month

950

Nos./Month

Collection, Storage &

reused for filling ETP

Sludge.

28.1 Residue &

Waste

0.12

MT/Month

-- 0.12

MT/Month




co-processing or


- Inorganic

Acids

0.9

MT/Month

-- 0.9

MT/Month

Collection, Storage &

Reused back in process.

31.1 Organic

Residue

-- 12.71

MT/Month

12.71

MT/Month




co-processing or


DETAILS OF DISPOSAL OF SOLID WASTES

Industry is a member of TSDF site of M/s. NECL (Nandesari Environment control Ltd.) for disposal of

hazardous wastes from time to time.

155

ANNEXURE-VII

DETAILS OF AIR POLLUTION CONTROL SYSTEM

DETAILS OF FUELCONSUMPTION

SR. NO. NAME OF FUEL QUANTITY

EXISTING ADDITIONAL TOTAL

1. LDO/Wood 0.28 KL/Day

(0.28 MT/Day)

5

KL/Day

5.28

KL/Day

2. Agro waste Briquettes/Coal --- 10 MT/Day 10 MT/Day

3. Diesel -- 30 Lit/Day 30 Lit/Day

DETAILS OF PROCESS VENT AND BOILER STACK

• EXISTING (FLUE GAS EMISSION THROUGH STACK)

Sr.

No.

Stack

Attached to

Stack Height in

meter

Air Pollution

Control Measure

Parameter Permissible Limit

1.

Boiler

15 -- PM

SOX

NOX

150 mg/Nm3

100 ppm

50 ppm

• EXISTING (PROCESS GAS EMISSION THROUGH STACK)

Sr.

No.

Stack

Attached to

Stack Height in

meter

Air Pollution

Control Measure


1.

2 Stage Scrubber

(Capacity = 500

Kg/Hr)

11

(From G.L.)

Scrubber

HCl

NH3

Cl2

20 mg/Nm3

175 mg/Nm3

09 mg/Nm3

• ADDITIONAL PROPOSED (FLUE GAS EMISSION THROUGH STACK)

SR.

NO.

TYPE OF

STACK

PARTICULAR STACK

HEIGHT

(M)

AIR EMISSION FUEL APCM

POLLUTANT CONC.

1. Thermic

Fluid

Heater (6

Lac Kcal)

STACK-1 30 PM

SO2

NOX

≤ 150

mg/NM3

≤ 100

LDO --

156

2. Steam

boiler-2 (3

TPH)

ppm

≤ 50

ppm

Agro

Waste

Multi

cyclone

Separator

with Bag

Filter

3 D.G. Sets

(250 KVA)

11

• ADDITIONAL PROPOSED (PROCESS GAS EMISSION THROUGH STACK)

Sr.

No.

Stack

Attached to

Stack Height in

meter

Air Pollution

Control Measure


1.

Reaction vessel 11 Two stage Alkali

scrubber

SO2

HCl

NH3

Bromine

< 40 Mg /NM3

< 20 Mg /NM3

< 3 PPM

• TOTAL AFTER EXPANSION

Sr.

No.

Stack

Attached to

Stack Height in

meter

Air Pollution

Control Measure


� (FLUE GAS EMISSION THROUGH STACK)

1.

Boiler -1

[Existing: LDO]

15

-- PM

SOX

NOX

150 mg/Nm3

100 ppm

50 ppm

2. Boiler -2

[3 MT/HRS]

[Proposed Agro

waste fuel ]

30 Multi cyclone

Separator with

Bag Filter

SPM

SOx

NOx

≤ 150 Mg/NM3

≤ 100 PPM

≤ 50 PPM

3 Thermic Fluid

Heater (6 Lac Kcal)

[LDO fuel]

-

3. D.G. Set

(250 KVA)

11 --

� (PROCESS GAS EMISSION THROUGH STACK)

1.

2 Stage Scrubber

(Capacity -500

Kg/Hr)

11

(From G.L.)

Scrubber

HCl

NH3

Cl2

20 mg/Nm3

175 mg/Nm3

09 mg/Nm3

157

2. Reaction vessel 11 Two stage Alkali

scrubber

SO2

HCl

NH3

Bromine

< 40 Mg /NM3

< 20 Mg /NM3

< 3 PPM

158

ANNEXURE-VIII

DETAILS OF HAZARDOUS CHEMICALS STORAGE & HANDLING

Sr.

No.

Name of the

Hazardous

Substance

Maximum

Storage

Mode of

Storage

Actual

Storage

State &

Operating

pressure &

temperature

Possible

type of

Hazards

1 Methanol 20 MT Tank 10 MT x 1 NTP Flammable/

Toxic

2 EDC/MDC 20 MT Tank 1 MT x 1 NTP Flammable/

Toxic

3 DMF 5 MT Drum Drum NTP Flammable/

Toxic

4 Toluene 20 MT Drum Drum NTP Flammable

5 Acetone 20 MT Tank 10 MT x 1 NTP Flammable

6 Ethyl Acetate 20 MT Tank 10 MT x 1 NTP Flammable

7 IPA 20 MT Drum Drum NTP Flammable

8 Bromine 1 MT Plastic

caret

3 kgs

Bottle / 6

No bottle

in 1 caret

NTP Toxic

9 Choloro

Sulphonic

acid

10 MT Tank 10 MT x 1 NTP Toxic

10 Liq Ammonia 20 MT Tank 10 MT x 1 NTP Toxic

11 Thyonil

chloride

5MT Drum Drum NTP Toxic

12 HCL 10 MT Drum Drum NTP Toxic

159

ANNEXURE – IX

SOCIO - ECONOMIC IMPACTS

1) Employment Opportunities

The manpower requirement for the proposed Expansion project is being expected to

generate some permanent jobs and secondary jobs for the operation and maintenance of

plant. This will increase direct / indirect employment opportunities and ancillary business

development to some extent for the local population.

This phase is expected to create a beneficial impact on the local socio-economic

environment.

2) Industries

Required raw materials and skilled and unskilled laborers will be utilized maximum from the

local area. The increasing industrial activity will boost the commercial and economical status

of the locality, to some extent.

3) Public Health

The company regularly examines, inspects and tests its emission from sources to make sure

that the emission is below the permissible limit. Hence, there will not be any significant

change in the status of sanitation and the community health of the area, as sufficient

measures have been taken and proposed expansion under the EMP.

4) Transportation and Communication

Since the existing factory is having proper linkage for the transport and communication, the

development of this project will not cause any additional impact. In brief, as a result of the

proposed expansion project there will be no adverse impact on sanitation, communication

and community health, as sufficient measures have been proposed expansion to be taken

under the EMP. The proposed expansion project is not expected to make any significant

change in the existing status of the socio -economic environment of this region.

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ANNEXURE-X

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PROPOSED TERMS OF REFERENCE FOR EIA STUDIES

1. Project Description

• Justification of project.

• Promoters and their back ground

• Project site location along with site map of 10 km area and site details providing various

industries, surface water bodies, forests etc.

• Project cost

• Project location and Plant layout.

• Water source and utilization including proposed water balance.

• Product spectrum (proposed products along with production capacity) and process

• List of hazardous chemicals.

• Mass balance of each product

• Storage and Transportation of raw materials and products.

2. Description of the Environment and Baseline Data Collection

• Micrometeorological data for wind speed, direction, temperature, humidity and rainfall

in 10 km area.

• Existing environmental status Vis a Vis air, water, noise, soil in 10 km area from the

project site. For SPM, RSPM, SO2, NOx.

• Ground water quality at 8 locations within 10 km.

• Complete water balance

3. Socio Economic Data

• Existing socio-economic status, land use pattern and infrastructure facilities available in

the study area were surveyed.

4. Impacts Identification And Mitigatory Measures

• Identification of impacting activities from the proposed expansion project during

construction and operational phase.

• Impact on air and mitigation measures including green belt

• Impact on water environment and mitigation measures

• Soil pollution source and mitigation measures

• Noise generation and control.

• Solid waste quantification and disposal.

5. Environmental Management Plan

• Details of pollution control measures

• Environment management team

• Proposed schedule for environmental monitoring including post project

6. Risk Assessment

• Objectives and methodology of risk assessment

• Details on storage facilities

161

• Process safety, transportation, fire fighting systems, safety features and emergency

capabilities to be adopted.

• Identification of hazards

• Consequence analysis through occurrence & evaluation of incidents

• Disaster Management Plan.

7. Information for Control of Fugitive Emissions

8. Post Project Monitoring Plan for Air, Water, Soil and Noise.

9. Information on Rain Water Harvesting

10. Green Belt Development plan

162

ANNEXURE-XI

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LAND POSSESIOM DOCUMENT (7/12/8-A COPY)

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164

165

166

167

ANNEXURE-XII

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CETP MEMBERSHIP CERTIFICATE (EICL)

168

169

ANNEXURE-XIII

______________________________________________________________________

TSDF & CHWIF MEMBERSHIP CERTIFICATE (NECL)

170

171

ANNEXURE-XIV

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TOPOSHEET

Documents

PROPOSED EXPANSION OF BULK DRUGS AND …environmentclearance.nic.in/writereaddata/Online/TOR/22...Construction, operation or decommissioning of the Project involving actions, which