€¦ · · 2016-12-31... (2-nitrophenyl) disulfide 2-Nitro benzene sulfanyl chloride Cl 2 Gas Material Balance Step-1 ... Chlorine gas 0.32 Recovered hexane 2.34 ... Material Balance

Product: -2-Nitro benzene sulfanyl chloride (NSC)

Route of synthesis

N+

O-

O

Cl

N+

O-

O

S

N+O

-

O

S

Sodium sullfideSulfur Trichloro ethylene

IodineN

+O-

O

SCl

2-Nitro benzene sulfanyl chloride1-chloro-2-nitrobenzene bis(2-nitrophenyl) disulfide

Cl2 Gas

Material Balance

Step-1

Input Kg Out put Kg

ONCB 2.85 Stage-1 1.40

Sodium sulfide 2.14 Recovered methanol 18.95

Sulfur 0.43 Vacuum loss of methanol 1.00

Methanol 19.95 aq, layer contain

Water 6.84 1) Water 6.68

2) Sodium chloride 1.60

3) Sodium sulfide 0.73

Residue after mL distillation 1.39

Hydrogen sulfide 0.46

Total 32.21 32.21

Step-2

Trihloro

ethylene 25.60 Finished product 1.00

Stage-I 1.40 Recovered trichloro ethylene 25.34

Iodine 0.75 Vapour loss to trichloroethylene 0.26

Chlorine gas 0.32 Recovered hexane 2.34

Hexane 2.46 Vapour loss of hexane 0.12

Residue after Hexane recovery 0.72

Iodine recovered 0.75

Total 30.53 30.53

Process flow diagram

Product: NSC Stage-01

Aqueous high TDS-10.86L. Recovered Methanol 98% Solid waste

Residue after mL distillation -1.39kg.

Reaction

ONCB-2.85kg. Sodium sulfide-2.14kg. Sulfur-0.43kg. Methanol – 19.95kg. Water-6.84kg.

Extraction and solvent distillation

Material isolation

Output- 1.40 kg.

Product: NSC Stage-II

Aqueous -NA. Recovered trichloro ethylene 98% Recovered hexane 98% Recovered Iodine 98% Solid waste

Residue after Hexane recovery-0.72kg.

Reaction

Trihloro ethylene-25.60kg. Stage-I-1.40kg. Iodine-0.75kg. Chlorine gas – 032kg. Hexane-2.46kg.


Material isolation

Output- 1.0 kg.

Product: -Chlorothymol

Route of synthesis

OH OH

ClSO2Cl

2

CCl3

Material Balance

Input Kg Out put Kg

Thymol 1.39 Chlorothymol 1.00

Sulfuryl chloride 1.50 Recovered CTC 3.13

Carbon tetra chloride 3.19 CTC Loss in vacuum 0.06

Sodiumcarbonate 0.24 Pet ether recovery 0.42

Pet ether 0.47 Pet ether loss 0.05

DM water 1.03 Sulfor diaoxide 0.59

Hydrochloric acid 0.34

Carbon dioxide 0.10

Aq. Layer contains

1) Water 1.01

2) Sodium sulfate 0.27


4) HCl 0.05

Residues after HVD & Solvent recovery 0.79

Total 7.83 7.83


Product: Chlorothymol

CO2 + SO2 +HCl gas (Scrubber)

Aqueous high TDS-2.14L. Recovered CTC 98% Recovered pet ether 98% Solid waste

Residues after HVD & Solvent recovery-0.79kg.

Reaction

Thymol-1.39kg. Sulfuryl chloridel-1.50kg. Carbon tetra chloride-3.19kg. Sodiumcarbonate-0.24kg. Pet ether-0.47kg. DM water- 1.03kg.


Material isolation

Output- 1.0 kg.

Product: -Sharpless catalyst

Route of synthesis

N

N

Cl

Cl

+N

NN

H

HH

O

O

N

H

H

H

O

O

ClH2N

H

H

H

OH

O

2

N

H

H

H

OH

O

Dichloro phthalylhydrazine

MDC

Ammonia Toluene

KOH; K2CO3

(S)-(6-methoxyquinolin-4-yl) (2R,4S,5R)-5-ethyl-1-azabiclo 2.2.2 oct-2-yl methanol. HCl

(S)-(6-methoxyquinolin-4-yl) (2R,4S,5R)-5-ethyl-1-azabiclo 2.2.2 oct-2-yl methanol

Sharpless catalyst

Material Balance

Step-1

Input Kg Out put Kg

Dihydroquinidine HCl 1.75 Dihydroquinidine Base 1.40

Ammonium hydroxide(25%) 11.29 Aq. Layer contain

MDC 10.83 1) Water 8.56

2) Ammonium chloride 0.26

3) Dissolved ammonia 2.65

4) Dihydroquinidine Base 0.17

MDC Recovered 10.29

MDC Loss in vacuum 0.54

Total 23.88 23.88

Step-2

Dihydroquinidine Base 1.40 Product 1.00

Dichloro phthalazine 0.44 Recovered Toluene 12.02

Toluene 12.14 Recovered Acetone 44.20

Potassium carbonate 0.89 Recovered IPA 9.06

Potassium hydroxide 0.36 Toluene loss 0.12

HCl Gas 0.08 IPA Loss 0.18

IPA 9.25 Acetone Loss 2.33

Acetone 46.53 Aq. Layer contain

Sodium bicarbonate 1.18 1) water 12.13

Water 11.76 2) Sodium chloride 0.49

3) potassium chloride 1.36

4) ureacted dichloro phthalazine 0.01

5) Sodium bicarbonate 0.45

CO2 evolved 0.65

84.01 84.01


Product: Sharpless catalyst Stage-01

Aqueous high TDS-11.64L. Recovered DCM 98%

Solid waste-NA

Reaction

Dihydroquinidine HCl-1.75kg. Ammonium hydroxide (25%)-11.29kg. MDC-10.83kg.


Material isolation

Output- 1.40 kg.

Product: Sharpless catalyst Stage-II

CO2 (Scrubber)

Aqueous high TDS-14.44L. Recovered Toluene 98% Recovered Acetone 98% Recovered IPA 98%

Solid waste-NA

Reaction

Dihydroquinidine Base-1.40kg. Dichloro phthalazine-0.44kg. Toluene-12.14kg. Potassium carbonate-0.89kg. Potassium hydroxide-0.36kg. HCl Gas-0.08kg. IPA-9.25kg.

Acetone-46.53kg.

Sodium bicarbonate-1.18kg. Water-11.76kg.


Material isolation

Output- 1.0 kg.

Product: - DOTA for Gadoteric acid

Route of synthesis:-

N

N

N

NO

OH

O

OH

O

OH

O

OH

NH

NH

NH

NH

O

OH

Cl

1) Chloro acetic acid; NaOH

1,4,7,10-Tetra azacyclo dodecane -1,4,7,10-Tetra acetic acid (DOTA)

ClH

ClH

2) HCl

Material Balance

Material Input in Kg Material Out-out in

Kg

Cyclane 0.66 DOTA HCl 1.00

Chloroacetic acid 1.45 Aq. Layer contain

Sodium hydroxide 0.99 Water 9.07

Hydrochloric acid 30% 2.27 Sodium chloride 1.44

Water 7.04 DOTA HCl 0.82

HCl 0.06

Total 12.40 Total 12.40


Cyclane 0.66 kg

Chloroacetic acid 1.45 kg

Sodium hydroxide 0.99 kg

Hydrochloric acid 30% 2.27 kg

Water 7.04 kg

Water 9.07 kg

MLR Sodium chloride 1.44 kg

DOTA HCl 0.82 kg

HCl 0.06 kg

out put

1.0 kg

Reaction

workup and

purification

Filter

Product:-Iopamidol


NH2

COOHHOOC

NH2

COOHHOOC

I I

I

KCl / ICl

Water

NH2

I I

I O

Cl

O

ClTEA/SOCl 2

MDC

O

O

ONH

I I

I O

Cl

O

Cl

DMA

Cl

O

O

O

+

+

DMA/TEAO

O

O

NH

I I

I OOOH

OHNH

OH

OHNH

OH OH

NH2

NH4OH

O

OH

NH

I I

I OOOH

OHNH

OH

OHNH

Stage II

Stage III

Stage I

Stage IV

Stage V

Cl

O

O

O

OH

O

O

O

OH

O

OH

O

Cl

- HCl

- HCl

-SO2

Acetoxy lactic acid chloride

Material Balance

O-Acetyl. Lactic acid chloride Stage-I

Input Kg Out put Kg

Lactic acid (90%) 1.12 Stage-I intermediate 0.82

Acetyl chloride 1.44 HCl gas 0.67

Acetic acid 0.37

Residue after HVD 0.68

Total 2.56 2.54

O-Acetyl. Lactic acid chloride Stage-II

Stage-I intermediate 0.82 Product 0.78

Thionyl chloride 1.37 SO2 gas 0.73

Dichloro methane 7.62 HCl Gas 0.61

DMF 0.02 MDC Vacuum loss 0.76

Water consumed by Th.Chloride 0.09 Recovered MDC 6.86

Residue after HVD 0.18

Total 9.91 9.91

Iopamidol Stage-I

Input Quantity

in Kg Out put

Quantity

in Kg

5-Amino isophthalic acid 0.54 Stage-I intermediate 1.37

Water 24.78 Aq. Effluent contains

Sodium chloride 0.92 1) Water 25.63

Sodium chlorate 0.17 2) NaCl 1.05

Sodium bisulfite 0.08 3) HCl 0.27

Iodine 1.14 4) Sodium chorate 0.08

30% HCl 1.09 5) Dissolved Sulfordioxide 0.05

6) Mono & Di iodo products 0.26

Total 28.71 28.71

Iopamidol Stage-II

Input Quantity

in Kg Out put

Quantity

in Kg

Stage-I intermediate 1.37 Stage-II intermediate 1.23

MDC 4.54 Recovered toluene 2.35

Triethyl amine 0.48 Recovered MDC 4.31

Thionyl chloride 1.69 Recovered Ethyl acetate 14.43

Ethyl acetate 14.73 Solvents/Gases to scrubber

Toluene 2.37 Solvents 0.55

Sodium bicarbonate 0.51 SO2 gas to scrubber 0.91

Sodium chloride 0.75 HCl Gas to scrubber 0.52

Sodium sulfate 0.27 CO2 Gas 0.27

Hyflo 0.07 Solid waste

Activated carbon 0.07 1) Activated carbon 0.07

Water 9.62 2) Sodium Sulfate 0.27

3) Hyflo 0.07

4) Residues after solvent recovery 0.00

Aq. Effluent contains

1) Water 9.73


3) Triethyl amine HCl 0.65

Total 36.46 36.46

Iopamidol Stage-III

Input Quantity

in Kg Out put

Quantity

in Kg

Stage-II intermediate 1.23 Stage-III intermediate 1.27

Acetoxy propionyl

chloride 0.78 Recovered Ethyl acetate 12.07

Dimethyl acetamide 1.23 Recovered toluene 1.22

Toluene 1.23 Recovered MDC 6.86

Water 24.62 Recovered acetic acid 0.37

Ethyl Acetate 12.31 Solvents/Gases to scrubber

Sodium sulphate 0.25 1) Ethyl acetate 0.25

Activated Charcoal 0.06 2) MDC 0.76

Sodium bicarbonate 0.49 3) Toluene 0.01

Hyflo 0.06 4) Carbon dioxide 0.26

Sodium chloride 1.02 Solid waste

Lactic acid 1.12 1) Sodiun sulfate 0.25

Acetyl chloride 1.44 2) Hyflo 0.06

thionyl chloride 1.37 3) Activated charcoal 0.06

MDC 7.62 Residues aftersolvent recovery/HVD 0.85

DMF 0.02 Aq. Effluent contains

Scrubber water for

acetoxy 11.28 1) Water 36.55

Caustic for scrubber 1.13 2) sodium bisulfite 1.19

3) Stage-I 0.17

4) O-Acetyl lactic acid 0.44

5) Dimethyl acetamide 1.23


7)DMF 0.02


Iopamidol Stage-IV

Input Quantity

in Kg Out put

Quantity

in Kg

Stage-III 1.27 Stage-IV 1.34

Serinol 0.41 Recovered methanol 5.25

DMA 9.58 Recovered Isopropanol 11.37

Triethyl amine 0.66 Recovered DMA 9.49

Methanol 5.53 Solvents/Gases to scrubber

Isopropanol 11.97 Methanol 0.28

Activated Charcoal 0.06 Isopropanol 0.60

Hyflo 0.19 Triethyl amine 0.30

DMA 0.10

Solid waste

Activated carbon 0.06

Hyflo 0.19

Triethyl amine hydrochloride 0.49

Residues aftersolvent recovery/HVD 0.21

Total 29.67 29.67

Iopamidol Stage-V

Input Quantity

in Kg Out put

Quantity

in Kg

Stage-IV 1.34 Iopamidol 1.00

25% Ammonia 2.01 Distilled water 16.21

Water 14.87 Recovered methanol 2.52

Methanol 2.65 Recovered Isopropanol 3.66

Isopropanol 3.70 Solvents/Gases to scrubber

Hyflo 0.20 Methanol 0.13

Isopropanol 0.04

Ammonia 0.47

Water 0.16

Solid waste

Hyflo 0.20

Residues aftersolvent recovery/HVD 0.18

Second crop 0.19

Total 24.77 24.77


Stage-1

Purified water 24.78 kg

Sodium chloride 0.92 kg

Iodine crystals 1.14 kg

Conc. Hydrochloric acid 1.09 kg

Sodium chlorate 0.17 kg

Purified water

Purified water

5-Amino isophthalic acid 0.54 kg Reaction

Water Water 25.62 kg

Filter NaCl 1.05 kg

sodium bisulphite 0.08kg HCl 0.27 kg

Sodium chorate 0.08 kg

Dissolved Sulfordioxide 0.046 kg

Mono & Di iodo products 0.25 kg

OUT PUT

1.37 kg

Filter

Reaction

Stage-2

MDC 4.54 kg

Triethyl amine 0.48 kg

Distilled water 9.62 kg

Thionyl chloride 1.69 kg

Stages-I 1.37 kg

Reaction

Solvents 0.54kg

SO2 gas to scrubber 0.90 kg

HCl Gas to scrubber 0.52 kg

Ethyl acetate 14.73 kg CO2 Gas 0.27 kg

Sodium bicarbonate 0.51 kg

Sodium chloride 0.75 kg Workup and

distillation

Water 9.62 kg

Recovered MDC 4.31 kg

Water 9.73 kg


Sodium sulfate 0.27 kg Triethyl amine HCl 0.65 kg

Hyflo 0.07 kg Filter

Activated carbon 0.07 kg Activated carbon 0.07 kg

Sodium Sulfate 0.27 kg

Hyflo 0.07 kg

Residues after solvent recovery 0.004 kg

Toluene 2.37 kg

Recovered toluene 2.35 kg

Recovered Ethyl acetate 14.43 kg

OUT PUT

1.23 kg

Distillation and

workup

Stage-3

Dimethyl acetamide 1.23 kg

Stage-II intermediate 1.23 kg

Acetoxy propionyl chloride 0.775 kg

Reaction

Ethyl Acetate 12.31 kg



Sodium sulphate 0.25 kg Workup

Activated Charcoal 0.06 kg

Ethyl acetate 0.25 kg

MDC 0.76 kg

Toluene 0.01 kg

Carbon dioxide 0.26 kg

Toluene 1.23 kg Distillation

Recovered Ethyl acetate 12.06 KG


Toluene Filter

Toluene

Out put

1.27 kg

Stage-4

DMA 9.58 kg

Stage-III 1.27 kg Reaction


Serinol 0.40 kg

Filter

Triethyl amine hydrochloride 0.49 kg

DMA 0.095 kg

Methanol 5.53 kg Distillation

Recovered DMA 9.48 kg

Activated Charcoal 0.06kg


Methanol

Activated carbon 0.06 kg

Hyflo 0.19 kg

Methanol 0.28 kg

Methanol Distillation

Isopropanol 11.97 kg

Recovered methanol 5.25 kg

Isopropanol Filter

Dryer

Methanol

Isoprpanol Reactor

Isoprpanol Filter

Dryer

out put

1.34 kg

Stage-5

Ammonia 0.47 kg

Water 0.16 kg

25% Ammonia 2.0 kg

Water 14.87 kg Reaction

Stage-IV 1.34 kg


pass 2 time through IPDA 522

IPDA522

pass 2 time through IPDB068

IPDB068

pass 5 time through IPDPA008

IPDPA008

Water

Hyflo 0.2 kg Filter

Hyflo 0.2 kg

Water 0.16 kg

Distillation


Isopropanol 0.037 kg scrubber loss

Water

Methanol Work up

Isoprpanol

Isoprpanol Filter Recovered Isopropanol from ML 3.6 KG

Out put

Dryer

1.0 kg

PFD for Acetoxy propionyl chloride

Stage-1

HCl gas 0.67 kg

Lactic acid (90%) 1.11kg

390 g Acetyl chloride 1.44 kg Reaction

Acetic acid 0.37 kg

Residue after HVD 0.68 kg

High vacuum

distillation


OUTPUT

0.82 KG

Stage-2

SO2 gas 0.73 kg

HCl Gas 0.61 kg

MDC loss 0.76 kg

Methylene dichloride 7.62 kg

Stage-I 0.82 kg Reaction

Dimethyl formamide 0.015 kg



High vacuum

distillation


OUTPUT

0.78 KG

Product:-Iohexol


NH2

Cl

OO

Cl

I

I I

NH

Cl

O

O

Cl

I

I I

O

NH2 OH

OH

DMA

AcCl

DMA/LiOH

Iohexol

NH

NH

OO

NH

OHOH

OH

OH

I

I I

O

N

NH

OO

NH

OHOH

OH

OH

I

I I

O

OH

OH

Cl

OH

OHMeOH/LiOH

N

NH

O O

NH

O

O

O

O

I

II

OO

O

crude

Triketal

N

NH

O O

NH

OH

OH

OH

OH

I

II

OOH

OHIohexol

Pure

2,4,6-triiodo-5-amino isophthalicacid dichloride

Stage-2

Stage-1

Stage-3a

Stage-6

NH2

Cl

OO

Cl

I

I I

NH2

OH

OO

OH

I

I I

NH2

OH

OO

OH I2-NaOCl

3-HCl


SOCl2

MDC

Stage-3b

Stage-4

Stage-5

triethyl amine

Material Balance

Stage-1

Input Quantity

in Kg Out put

Quantity

in Kg









Total 29.35 29.35

Stage-2

Input Quantity

in Kg Out put

Quantity

in Kg













3) Hyflo 0.07



1) Water 9.95



Total 37.27 37.27

Stage-3

Input Quantity

in Kg Out put

Quantity

in Kg

2,4,6-triiodo-5-amino isophthalic acid dichloride

1.26 Stage-III intermediate 1.28

Acetyl chloride 0.27 Recovered dimethyl acetamide 9.35

Dimethyl acetamide (DMA) 9.45 Recivered methanol 9.84

3-Amino propane Diol 0.52 Solid waste

Triethyl amine 0.90 TEA hydrochloride 1.31

Methanol 10.93 Residues after distillation of Methanol ML 0.48

Water 0.13 Solvents/Gases to scrubber

Methanol 1.09

Dimethyl acetamide 0.09

Total 23.45 23.45

Stage-4

Stage-III intermediate 1.28 Crude Iohexol 1.33

3-chloro-1,2-propane diol 0.38 Recovered methoxy ethoxy ethanol 3.80

Lithium hydroxide (Anhydrous) 0.08 Recovered Butanol 3.08

Methoxy ethoxy ethanol 3.84 Recovered water 10.04

Butanol 3.12 Solid waste

Conc. HCl 0.29 Activated carbon 0.03

Water 10.26 Hyflo 0.05

Activated carbon 0.03 Residues after distillation of Butanol ML 0.07

Hyflo 0.05 Solvents/Gases to scrubber

Water for resin wash 2.56 Methoxy ethoxy ethanol 0.04

Butanol 0.03

Water 0.51

Aq. Effluents containing

Water 2.56

Lithium chloride 0.15

3-chloro-1,2-propane diol 0.19


Stage-5

Crude iohexol 1.33 1.33

Dimethoxy propane 6.67 Recovered dimethoxy propane 6.10

PTSA 0.04 Recovered Methanol 0.25

sodium bicarbonate 0.03 Solvents/Gases to scrubber

Water 8.00 Dimethoxy Propane 0.06

Methanol 0.00

Water 0.80


Water 7.20

Sodium p-toluene sulfonate 0.05

Sodium bicarbonate 0.01

Iohexol & O-Alkyl iohexol 0.27

Total 16.07 16.07

Stage-6

Ketal 1.33 Product 1.00

Water 12.97 Distilled water 12.32

Sulfuric acid 0.05 Recovered IPA 7.92

Sodium hydroxide 0.03 Solvents/Gases to scrubber

Activated carbon 0.03 Water 0.65

Hyflo 0.07 IPA 0.08

Isopropanol 8.00 Acetone 0.25

Water for resin wash 2.67 Solid waste


Hyflo 0.07

Residue after IPA mL distillation 0.10


Water 2.67

Sodium sulfate 0.08



Stage-1






Purified water

Purified water



Filter NaCl 1.05 kg





OUT PUT

1.37 kg

Reaction

Filter

Stage-2

MDC 4.54 kg




Stages-I 1.37 kg

Reaction

Solvents 0.54kg






distillation Water 9.62 kg


Water 9.73 kg






Hyflo 0.07 kg


Toluene 2.37 kg



OUT PUT

1.256 kg

Distillation and

workup

Stage-3

Stage-II 1.256 kg

Acetyl chloride 0.27 kg


3-Amino propane Diol 0.52 kg

Triethyl amine 0.897 kg Reaction

Methanol 10.93 kg

Water 0.125 kg

DMA Filter TEA hydrochloride 1.3 kg


Methanol 1.09 kg

METHANOL distillation

WATER


Recovered dimethyl acetamide 9.35 kg

Residues after distillation of Methanol ML 0.48 kg

METHANOL Filter Methanol

out put

1.28 kg

Stage-4

Methoxy ethoxy ethanol 0.038 kg

Stage-III 1.28 kg

3-chloro-1,2-propane diol 0.38 kg

Lithium hydroxide (Anhydrous) 0.08 kg Reaction

Methoxy ethoxy ethanol 3.84 kg

Recovered methoxy ethoxy ethanol 3.8 kg

225H

Reaction mass pass through column two time

860



Hyflo 0.051 kg Filter Hyflo 0.051 kg

Water

Butanol 0.031 kg

Water 0.512 kg

Butanol 3.115 kg Distillation

Recovered Butanol 3.08 kg

Recovered water 10.03 kg

Residues after distillation of Butanol ML 0.075 kg

Under nitrogen Filter

Water 2.56 kg

Lithium chloride 0.15 kg

3-chloro-1,2-propane diol 0.19 kg

out put

1.33 kg

Stage-5

Dimethoxy propane 0.06 kg

Methanol 0.003 kg

Crude iohexol 1.33 kg

Dimethoxy propane 6.67 kg

PTSA 0.039 kg Reaction and distil lation

sodium bicarbonate 0.03 kg

Water 7.99 kg

Recovered dimethoxy propane 6.10 kg

Recovered Methanol 0.25 kg

Water Filter

Water 7.19 kg

Sodium p-toluene sulfonate 0.045 kg


Iohexol & O-Alkyl iohexol 0.27 kg

Water 0.799 kg

Out put

1.33 kg

Stage-6

Ketal 1.33 kg

water 12.97 kg

Sulfuric acid 0.052 kg Reaction


Water for resin wash 2.66 kg

225H


860




Water

Water 0.65 kg

butanol 0.079 kg

Acetone 0.25 kg

Butanol 8.0 kg Distillation


Recovered butanol 7.91 kg

Under nitrogen Filter

Water 2.66 kg

Sodium sulfate 0.076 kg

Out put

1.0 kg

Product:-Iodixanol


NH2

Cl

OO

Cl

I

I I

NH

Cl

O

O

Cl

I

I I

O

NH2 OH

OH

DMA

AcCl

DMA/LiOH

TEA (Optional)

NH

NH

OO

NH

OHOH

OH

OH

I

I I

O

Cl

O


Stage-2

Stage-1

Stage-3a

NH2

Cl

OO

Cl

I

I I

NH2

OH

OO

OH

I

I I

NH2

OH

OO

OH I2-NaOCl

3-HCl


SOCl2

MDC

Stage-3b

Stage-4

MeOH/NaOH

Cl

NH O

O

NHOH

OH

OH

OH

I

I

I

OOH

NNH

O

O NH

OH

OH

OH

OHII

IO

Iodixanol

Material Balance

Stage-I

Input Quantity

in Kg Out put

Quantity

in Kg









Total 32.17 32.17

Stage-II

Input Quantity

in Kg Out put

Quantity

in Kg













3) Hyflo 0.08

4) Residues after solvent

recovery 0.00


1) Water 10.90



Total 40.85 40.85

Stage-III

Input Quantity

in Kg Out put

Quantity

in Kg

Stage-II intermediate 1.38 Stage-III 1.41

Acetyl chloride 0.30 Recovered dimethyl acetamide 10.27

Dimethyl acetamide (DMA) 10.37 Recivered methanol 10.80

3-Amino propane Diol 0.57 Solid waste

Triethyl amine 0.99 TEA hydrochloride 1.43

Methanol 12.00

Residues after distillation of Methanol ML 0.53

Water 0.14 Solvents/Gases to scrubber

Methanol 1.20


Total 25.75 25.75

Stage-IV

Input Quantity

in Kg Out put

Quantity

in Kg

Stage-III intermediate 1.41 Iodixanol 1.00

2-methoxy ethanol 1.38

Recovered 2-methoxy ethanol+ water 3.56

Epichlorohydrin 0.05 Scrubber loss 0.04

Sodium hydroxide 0.09 Aq. Effluent containing

30% HCl 0.11 Water 0.60

Water 2.21 Sodium chloride 0.05


Stage-1

Water 27.76 kg


Iodine1.27 kg



Purified water

Purified water



Filter NaCl 1.18 kg

Sodium bisulfite 0.08 kg HCl 0.31 kg




OUT PUT

1.53 kg

Reaction

Filter

Stage-2

MDC 5.08 kg




Stage-I intermediate 1.53 kg

Reaction

Solvents 0.61 kg






distillation Water 10.78 kg


Water 10.9 kg






Hyflo 0.08 kg

Residues after solvent recovery

Toluene 1.87 kg



OUT PUT

1.38 kg

Distillation and

workup

Stage-3


Acetyl chloride 0.3 kg

Dimethyl acetamide (DMA) 10.37 kg

3-Amino propane Diol 0.57 kg


Methanol 12 kg

Water 0.14 kg

Reaction

DMA Filter TEA hydrochloride 1.43 kg


Methanol 1.2 kg

METHANOL distillation

WATER

Recivered methanol 10.8 kg


Residues after distillation of Methanol ML 0.53 kg

METHANOL Filter Methanol

out put

1.41 kg

Stage-4

Stage-III intermediate 1.41 kg

2-methoxy ethanol 1.38 kg

Sodium hydroxide0.09 kg

Epichlorohydrin 0.05 kg

30% HCl 0.11 kg

Water 2.21 kg Scrubber loss 0.04 kg

Reaction

Recovered 2-methoxy ethanol+ water 3.56 kg

Water 0.6 kg

Filter Sodium chloride 0.05 kg

out put

1.0 kg

Product:-Iopromide


+

O

ClO

Methoxy acetyl chloride

O

O

O

Cl

O Cl

NH

I

I

I

O

O

OCl

O

NHNH

II

I

OH

OH

OH

OH

NH2

DMA

N1,N3-bis(2,3-dihydroxypropyl)-5-

(2-hydroxyacetamido)-2,4,6-triiodobenzene-1,3-dicarboxamide

1-amino-2,3-propanediol

O

O

O

Cl

O

NH

NH

I

I IO

O

O

O

1) AcOH; H2SO

4

2) NaOAc

DMA

3-[3-(chlorocarbonyl)-2,4,6-triiodo-5-(2-methoxyacetamido)benzamido]propane-1,2-diyl diacetate

Stage-2Stage-1

NH2

Cl

OO

Cl

I

I I

NH2

OH

OO

OH

I

I I

NH2

OH

OO

OH I2-NaOCl

3-HCl SOCl

2

MDC

5-amino-2,4,6-triiodobenzene-1,3-dicarbonyl dichloride

+

3-[(2,3-dihydroxypropyl)carbamoyl]-2,4,6-triiodo-5-[(methoxyacetyl)amino]benzoyl chloride

OH

OH

NH1)

TEA

3-(methylamino)propane-1,2-diol

2) Aq. NaOH

Iopromide

O

O

O

O

NHNH

II

I

OH

OH

OH

OH

N

Stage-3a

Stage-3b

Stage-4

Stage-5

Material Balance

Stage-1

Input Quantity

in Kg Out put

Quantity in

Kg

5-Amino isophthalic acid 0.65 5-amino-2,4,6-

triiodoisophthalic acid 1.65








Total 34.72 34.72

Stage-2

Input Quantity

in Kg Out put

Quantity

in Kg

5-amino-2,4,6-triiodoisophthalic acid 1.65 5-amino-2,4,6-triiodoisophthalic

acid dichloride 1.49












3) Hyflo 0.08


recovery 0.00


1) Water 11.77



Total 44.09 44.09

Stage-3

Material Input in

Kg Material Output

in Kg

5-amino-2,4,6-triiodoisophthalic acid dichloride 1.49 Stage-3 intermediate 1.19

Dimethyl acetamide for stage-3a 1.87 Revovered MDC 26.74

Methoxy acetyl chloride 0.41 Recovered dimethyl acetamide 5.80

MDC 28.15 Scrubber loss

Water 2.34 Dimethyl acetamide 0.06

Sodium bicarbonate 0.11 MDC 1.41

Dimethyl acetamide 5.86 CO2 generated 0.06

Triethyl amine 0.21 Aq. Layer contain

Aminopropane diol 0.16 Water 2.36


Methoxy acetic acid 0.11

trithyl amine hydrochloride 0.29

Sodium chloride 0.08

DMA 1.87

Residues after Solvent recovery 0.59

Total 40.59 40.59

Stage-4

Material Input in

Kg Material Output

in Kg

Stage-3 intermediate 1.19 Stage-4 intermediate 1.20

Acetic acid 0.89 Aq. Layer contain

Sulfuric acid 0.02 water 11.64

Sodium acetate trihydrate 0.05 Sulfuric acid 0.02

Water 11.56 Acetic acid 0.71

Product 0.14


Stage-5

Material Input in

Kg Material Output in

Kg

Stage-4 intermediate 1.20 Iopramide 1.00

Dimethyl acetamide 2.01 Water recovered 1.48

Trethyl amine 0.32 Recovered DMA 1.99

Dihydroxy-n-methyl propyl amine 0.16 Scrubber loss

Sodium hydroxide 0.15 DMA 0.02

Water for hydrolysis 1.49 Water 0.01

Water for resin wash 2.98 Aq. Layer of resin wash contain

30% HCl for resin wash 0.45 water 3.42

Caustic for resin wash 0.13 Sodium chloride 0.52

triethyl amine 0.32

Product 0.12



Stage-1






Purified water

Purified water



Filter NaCl 1.27 kg





OUT PUT

1.65 kg

Reaction

Filter

Stage-2

MDC 5.49 kg kg




Stages-I 1.65 kg

Reaction

Solvents 0.66kg






distillation

Water 11.63 kg


Water 11.77 kg






Hyflo 0.08 kg


Toluene 2.37 kg



OUT PUT

1.49 kg

Distillation and

workup

Stage-3

5-amino-2,4,6-triiodoisophthalic acid dichloride 1.49 kg

Dimethyl acetamide for stage-3a 1.87 kg

Methoxy acetyl chloride 0.41 kg

MDC 28.15 kg

Water 2.34 kg Dimethyl acetamide 0.06 kg

Sodium bicarbonate 0.11 kg CO2 generated



Aminopropane diol 0.16 kg

Reaction


Water 2.34 kg

Hydrochloric acid 0.04 kg

Methoxy acetic acid 0.11 kg

trithyl amine hydrochloride 0.29 kg


DMA 1.87 kg

MDC 1.41 kg

Filter MLR

Revovered MDC 26.74 kg

Residues after Solvent recovery 0.59 kg

out put

1.19 kg

Stage-4

Stage-3 intermediate 1.19 kg

Acetic acid 0.89 kg

Sulfuric acid 0.02 kg

Sodium acetate trihydrate 0.05 kg

Water 11.56 kg

Reaction

Filter

water 11.64 kg

Sulfuric acid 0.02 kg

Acetic acid 0.71 kg

Product 0.14

out put

1.2 kg

Iopramide Stage-V



Trethyl amine 0.32 kg DMA vapours 0.02 kg

Dihydroxy-n-methyl propyl amine 0.16 kg


Reaction

and workup


Water for hydrolysis 1.49 kg cation exchange

Water for resin wash 2.98 kg column

30% HCl for resin wash 0.45 kg

anion exchange

Caustic for resin wash 0.13 kg column

Water vapous 0.01 kg

workup

and distillation

Water recovered 1.48 kg

Filter

water 3.42 kg


triethyl amine 0.32 kg

Product 0.12 kg

out put

1.0 kg

Product:-Ioversol


2

I

II

O

NH

O

NH

NH2

OH

OH

OH

OH

5-amino-N1,N3-bis(2,3-dihydroxy

propyl)-2,4,6-triiodobenzene-1,3-dicarboxamide

3-aminopropane-1,2-diol

I

II

O

NH

O

NH

NH2

O

OO

O

OOO

O

Ac2O

Pyridine

DMF

Na2CO3

I

II

O

NH

O

NH

NH

O

OO

O

OOO

O

O

O

O

DMA

1) MeOH-NaOH

2) Chloroethanolaq. NaOH

+Stage-2

Stage-1

NH2

Cl

OO

Cl

I

I I

NH2

OH

OO

OH

I

I I

NH2

OH

OO

OH I2-NaOCl

3-HCl SOCl

2

MDC


Stage-3

OH

OH

NH2

OHO

OH

Glycolic acid

1) acetyl chloride

OO

Cl

O 2) acetyl chloride

Stage-4

Stage-5

Stage-6II

I

O NH

O

NHN

OH

OH

OH

OH

OH

O

OH

Ioversol

Stage-1

Input Quantity

in Kg Out put

Quantity in

Kg

5-Amino isophthalic acid 0.83 5-amino-2,4,6-triiodoisophthalic acid 2.11








Total 44.23 44.23

Stage-2

5-amino-2,4,6-


5-amino-2,4,6-triiodoisophthalic acid

dichloride 1.90












3) Hyflo 0.11



1) Water 14.99



Total 56.18 56.18

Stage-3

Material Input in


Kg


Dimethyl formamide 3.55 Solid contains

Sodium carbonate 1.02 Sodium carbonate 0.17

3-amino-1,2-propane diol 0.73 Sodium chloride 0.93

Water 19.62 Recovered DMF 3.51

Conc. HCl 1.74 Recovered methanol 10.26

Ethyl acetate 7.85 Recovered Ethyl acetate 7.77

Methanol 10.47 Scrubber loss

Carbon dioxide 0.35

DMF 0.04

Methanol 0.21

Ethyl acetate 0.08

Aq. Layer contains

Water 20.84

Dissolved HCl 0.52

Stage-3 intermediate 0.91

3-amino-1,2-propane diol 0.15


Stage-4

Material Input in


Kg

Stage-3 1.13 Stage-4 intermediate 1.39

Pyridine 1.13 Recovered Ethyl acetate 4.32

Acetic anhydride 0.74 Scrubber loss

Ethyl acetate 4.36 Ethyl acetate 0.04

Water 6.55 Aq. Layer contains

30% HCl 0.65 water 7.00

Pyridine 1.13

hydrochloric acid 0.18

acetic acid 0.49

Total 14.56 14.56

Stage-5

Material Input in


Kg


Acetoxy acetyl chloride 0.65 Aq. Layer contains

Dimethyl acetamide 4.18 Water 19.93

Ethyl acetate 15.94 Acetoxy acetic acid 0.38

Water 19.93 Dimethyl acetamide 4.18

Recovered Ethyl acetate 15.78

hydrochloric acid 0.17

Stage-5 intermediate 0.21

Scrubber loss

Ethyl acetate 0.16


Stage-6

Material Input in


Kg

Stage-5 intermediate 1.28 Ioversol 1.00

Methanol 6.97 Recovered methanol 6.83

Water 10.13 Recovered water 10.03

Chloroethanol 0.35 Scrubber loss

Sodium hydroxide 0.44 Ethylene oxide 0.19

Methanol 0.14

Water 0.10

Solid residue after mL recovery 0.88

19.18 19.18

Stage-1

Purified water 38.17 kg kg


Iodine crystals 1.75kg



Purified water

Purified water



Filter NaCl 1.62 kg





OUT PUT

2.11 kg

Reaction

Filter

Stage-2

MDC 6.99kg kg


Water 14.82 kg


Stages-I 2.11 kg kg

Reaction

Solvents 0.84 kg



Ethyl acetate 22.69 kg CO2 Gas0.41 kg



Workup and

distillation

Water 14.82 kg


Water 14.99 kg


Sodium sulfate 0.42 kg Triethyl amine HCl ,1 kg




Hyflo 0.11


Toluene 3.65 kg



OUT PUT

1.9 kg

Distillation and

workup

Stage-3

5-amino-2,4,6-triiodoisophthalic

acid dichloride 1.9 kg

Dimethyl formamide 3.55 kg

Sodium carbonate 1.02 kg

3-amino-1,2-propane diol 0.73 kg

Methanol 10.47 kg

Carbon dioxide 0.35 kg


Filter Sodium chloride 0.93 kg


DMF 0.04 kg

Methanol vapours 0.21 kg


Water 19.62 kg work up

Conc. HCl 1.74 kg and distillation



Recovered DMF 3.51 kg

Water 20.84 kg

Dissolved HCl 0.52 kg


out put 3-amino-1,2-propane diol 0.15 kg

1.13 kg

Stage-4

Stage-3, 1.13 kg

Pyridine 1.1 3kg

Acetic anhydride 0.74 kg Ethyl acetate 0.04 kg


Water 6.55 kg

30% HCl 0.65 kg

Reaction


Filter

water 7 kg

Pyridine 1.13 kg

hydrochloric acid 0.18 kg

acetic acid 0.49 kg

out put

1.39 kg

Stage-5


0.65 kgAcetoxy acetyl chloride

Dimethyl acetamide 4.8 kg Ethyl acetate 0.16 kg


Water 19.93 kg

Reaction

Water 19.93 kg

Acetoxy acetic acid 0.38 kg



out put hydrochloric acid 0.17 kg

1.28 kg Stage-5 intermediate 0.21 kg

Stage-6


Methanol 6.97 kg Ethylene oxide vapours 0.19 kg

Water 10.13 kg Methanol vapours 0.14 kg

Chloroethanol 0.35 kg Water vapours 0.1 kg


Reaction


Recovered water 10.03 kg

Filter Solid residue after mL recovery 0.88 kg

MLR recovery

out put

1.0 kg

Product:-Iomeprol


+

O

ClO O

2-chloro-2-oxoethyl acetate

O

O OO

Cl

OCl

NH

I

I

I

O

OH

O

NH

O

NH

NH

I

I I

OH

OH

OH

OH

2) NaOH

1)

O

OH

O

NH

ONH

N

I

I

IOH

OH

OH

OH

DMA/ Methyl bromide

DMA

DMA

Iomeprol

N1,N3-bis(2,3-dihydroxypropyl)-5-

(2-hydroxyacetamido)-2,4,6-triiodobenzene-1,3-dicarboxamide

1-amino-2,3-propanediol

2-[3,5-bis(chlorocarbonyl)-2,4,6- triiodoanilino]-2-oxoethyl acetate

+Stage-2

Stage-1

NH2

Cl

OO

Cl

I

I I

NH2

OH

OO

OH

I

I I

NH2

OH

OO

OH I2-NaOCl

3-HCl SOCl

2

MDC


OH

OH

NH2

Stage-3

Stage-4

Stage-5

Material balance

Stage-1

Input Quantity

in Kg Out put

Quantit

y in Kg

5-Amino isophthalic acid 0.43 5-amino-2,4,6-









Total 22.61 22.61

Stage-2

Input Quantity

in Kg Out put

Quantity

in Kg

5-amino-2,4,6-


5-amino-2,4,6-triiodoisophthalic

acid dichloride 0.97












3) Hyflo 0.05


recovery 0.00


1) Water 7.66



Total 28.72 28.72

Stage-3

Material Input in

Kg Material Output

in Kg


Dimethyl acetamide 3.88 Recovered DMA 3.84

Acetoxy acetyl chloride 0.55 Scrubber loss

Water 7.76 DMA scrubber loss 0.02

Water 0.19

HCl Gas to scrubber 0.15


Water 7.56


Acetoxy acetic acid 0.29


Stage-4

Material Input in

Kg Material Output

in Kg


Dimethyl acetamide 7.20 Recovered DMA:water 20.05

2,3-dihydroxy propyl amine 0.72 Scrubber loss

Water 13.05 DMA:Water 0.20

Sodium hydroxide 0.07 Aq. Resin Column wash effluent contain

Water for resin column wash 11.25 Water 11.35

Sodium acetate 0.15

2,3-dihydroxy propyl amine 0.58


Step-5

Material Input in

Kg Material Output

in Kg

Stage-4 intermediate 1.06 Iomeprol 1.00

Dimethyl acetamide 8.21 Recovered DMA, Methanol &

Water 9.33

Sodium hydroxide 0.01 Scrubber loss Methanol 1.58 DMA, Methanol & Water 0.49

Methy bromide 0.22 Methyl bromide 0.09

Water for resin wash 5.28 Aq. Resin Column wash effluent contain

30% Hydrochloric acid for resin wash 0.02 Water 5.30

Sodium chloride -0.07

Sodium bromide 0.14

Iomeprol 0.10



Stage-1



Iodine crystals 0.89kg



Purified water

Purified water


Water 1) Water 20.19 kg

Filter 2) NaCl 0.83kg

sodium bisulphite 0.06kg 3) HCl kg

4) Sodium chorate 0.07 kg

5) Dissolved Sulfordioxide 0.04 kg

6) Mono & Di iodo products 0.2 kg

OUT PUT

1.08kg

Reaction

Filter

Stage-2

MDC 3.57 kg




Stages-I 1.08 kg

Reaction

Solvents 0.43kg


HCl Gas to scrubber 0.41kg




distillation

Water 7.58 kg


Water 7.66 kg






Hyflo 0.05 kg


Toluene 1.87 kg



OUT PUT

0.97 kg

Distillation and

workup

Stage-3

stage-II, 0.97 Kkg


Acetoxy acetyl chloride 0.55 kg

water 7.76 kg

DMA scrubber loss 0.02 kg

Water 0.19 kg


Reaction


Water 7.56 kg

Filter Dimethyl acetamide 0.02 kg

Acetoxy acetic acid 0.29 kg

out put

1.10 kg

Stage-4



2,3-dihydroxy propyl amine 0.72 kg

water 13.05 kg


Reaction

and workup

Water for resin column wash 11.25 kg cation exchange

column

anion exchange

column

DMA:Water vapours 0.20 kg

workup

DMA:Water vapours 20.05 kg

Filter

water 11.35 kg

Sodium acetate 0.15 kg

2,3-dihydroxy propyl amine 0.58 kg

out put

1.06 kg

Stage-5



Sodium hydroxide 0.01 kg DMA, Methanol & Water 0.49 kg

water 13.05 kg

methanol 1.58 kg

Methy bromide 0.22 kg Reaction

and workup

DMA, Methanol & Water 9.33 kg

Water for resin wash 5.28 kg cation exchange

30% Hydrochloric acid for resin wash

0.02 kg column

anion exchange water 5.30 kg

column sodium chloride 0.07 kg

sodium bromide 0.10 kg

Iomeprol 0.10 kg

Water vapours

distillation

Water distilled

Filter

out put

1.00 kg

Product:-Gadoterate meglumine


N

N

N

NO

OH

O

OH

O

OH

O

OH1,4,7,10-Tetra azacyclo dodecane -1,4,7,10-Tetra acetic acid (DOTA)

ClH

OH

NH

H OH

H OH

OH H

H OH

+

Meglumine

Gd2O

3+N

N

N

NO

OH

O

OH

O

OH

O

OH

Gd3+

OH

NH

H OH

H OH

OH H

H OH

Gadoterate meglumine

Material Balance

Material Input in Kg Material Out-put in Kg

1,4,7,10-Tetra azacyclo dodecane -1,4,7,10-Tetra acetic acid (DOTA)

0.15 Gdotarate meglumine solution 1.00

Meglumine 0.07

Gadolinium oxide 0.07

Water 0.71



1,4,7,10-Tetra azacyclo dodecane -1,4,7,10-Tetra acetic acid (DOTA) 0.15 Kg

Meglumine 0.07 Kg

Gadolinium oxide 0.07 Kg

Water 0.71 Kg

Gadoterate miglumine

1 Kg

No effluents

Reactor Filter

Product:- Paroxetine Hydrochloride


N

F

O S

O

O

O

OOH

SesamolNaOH

Tosylate

ClH

Stage-II

S

O

OCl

MDC

TEA

N-methyl paroxetine

Stage-III

Phenyl chloroformate

Toluene

Carbamate

NaOH-Toluene

Paroxetine Hydrochloride hemihydrate

1/2 H2O

IsopropanolParoxetine hydrochloride hemi hydrate(Pure)

+

N

OH

F

Tosyl chloride

Stage-I

HCl

S-Carbinol

N

O

F

O

O

O

O

Cl+

N

O

F

O

O

O

O

Toluene

NH

O

F

O

O

Material Balance

Stage-I

Input Kg Out put Kg

S-Carbinol 1.23 Stage-I intermediate 1.77

Tosyl chloride 1.31 Recovered MDC 15.15

Triethyl amine 0.85 Recovered Hexane 3.37

Dimethylamino pyridine 0.05 Solvent loss to vacuum 0.98

Sodium bicarbonate 0.46 Aq. Layer containing

Sodium sulphate 0.38 1) Water 19.78

Methylene dichloride (MDC) 15.95 2) sodium para toluene sulfonate 0.27

Hexane fraction 3.55 3) Sodium chloride 0.24

Purified water 19.68 4) triethyl amine 0.85

5) Hydrochloric acid 0.05

CO2 gas to atmosphere 0.24

Solid waste

sodium sulfate 0.38

Residue after Hexane recovery 0.37

Total 43.46 43.46

Stage-II

(-)-Tosylate 1.77 Stage-II intermediate 1.31

Sodium hydroxide flakes 2.74 Recovered toluene 5.94

Sesamol 0.71 Recovered Hexane 3.35

Toluene 6.00 Solvent loss to vacuum 0.24

Tetrabutyl ammonium bromide 0.06 Aq. Layer containing

Hexane fraction 3.52 1) Water 21.49

Water 21.49 2) sodium para toluene sulfonate 0.91

3) Sodium hydroxide 2.55

4) Tetrabutyl ammonium bromide 0.06

Solid residue after hexane distillation 0.45

Total 36.29 36.29

Stage-III

Input Kg Out put Kg

(-)-N-methyl Paroxetine 1.31 Stage-III intermediate 1.38

Phenyl chloroformate 0.65 Recovered toluene 9.00

Toluene 9.10 Recovered Hexane 3.45

N,N-Di-isopropyl ethylamine 0.10 Solvent loss to vacuum 0.27

Sulphuric acid 0.38 Methyl chloride to scrubber 0.19

Hexane fraction 3.63 Aq. Layer containing

Sodium sulphate 0.38 1) Water 8.70

Water 8.70 2) Sulfuric acid 0.38

3) N,N-Di-isopropyl ethyl amine 0.10

Solid waste containing

1) Sodium sulfate 0.38

2) Oily residue to insinarator 0.32

3) Residue after hexane ML distillation 0.06

Total 24.25 24.25

Stage-IV Carbamate 1.38 Crude paroxetine 1.08

Sodium Hydroxide flakes 0.581175 Recovered toluene 10.13

Toluene 10.23283 Recovered Hexane 0.58

Activated carbon 0.076875 Solvent loss to vacuum 0.13

Hydrochloric acid (min.33%) 0.572565 Aq. Layer containing

Methanol 0.24354 1) Water 10.62

Hyflo 0.083025 2)Sodium hydroxide 0.58

Hexane 0.60885 3) Phenol 0.29

Water 10.24 Carbondioxide to atmosphere 0.14

Solid reside contains

1) Hyflo 0.08

2) Activated carbon 0.08

3) Residue after hexane ML distillation 0.32

Total 24.02 24.02

Stage-V Crude Paroxetine 1.08 Pure paroxetine 1.00

Isopropanol 5.92 Recovered IPA 5.80

Solvent loss to vacuum 0.12

Residue after IPA recovery 0.08

Total 7.00 7.00


Product: Paroxetine Stage-01

CO2 (Scrubber)

Aqueous high TDS 21.19 L Recovered MDC 98% Recovered Hexane 98%

Solid waste

(Sodium sulphate 0.38 Kg.) (Residue of hexane0.37 Kg.)

Reaction

S-Carbinol- 1.20 Kg. Tosyl chloride- 1.31 Kg Triethylamine-0.85 Kg Sodium bicarbonate0.46 Kg. Sodium sulphate-0.38Kg. MDC-15.95 Kg. Hexane fraction-3.55 Kg. Purified water-19.68 kg.


Material isolation

Output-1.77 Kg

Product: Paroxetine Stage-II

Aqueous high TDS 25.01 L Recovered Toluene 98% Recovered Hexane 98%

Solid waste (Solid residue after hexane distil.0.45kg)

Reaction

(-)-Tosylate- 1.77 Kg. Sodium hydroxide flakes-2.74Kg Sesamol-0.71 Kg Toluene-6.0 Kg. Tetrabutyl ammonium bromide-0.06 kg. Hexane fraction-15.95 Kg. Hexane fraction-3.92 Kg. Water-21.19 kg.


Material isolation

Output-1.31 Kg

Product: Paroxetine Stage-III

Aqueous high TDS 9.18 L Recovered Toluene 98% Recovered Hexane 98% Methyl chloride to scrubber 0.19 kg.

Solid waste Sodium sulphate-0.38 kg. Oily residue to incinerator-0.32 kg. Residue after hexane ML distillation0.06kg.

Reaction

(-)-N-methyl Paroxetine- 1.31 Kg. Phenyl chloroformate-0.65 Kg Toluene-9.10 Kg N, N-Di-isopropyl ethylamine-0.10 Kg. Sulphuric acid-0.38 kg. Hexane fraction-3.63 Kg. Sodium sulphate-0.38 Kg. Water-8.70 kg.


Material isolation

Output-1.38 Kg

Product: Paroxetine Stage-IV

CO2 (Scrubber)

Aqueous high TDS 11.49 L Recovered Toluene 98% Recovered Hexane 98% Methyl chloride to scrubber 0.19 kg.

Solid waste Hyflo-0.08 kg. Activated carbon-0.08 kg. Residue after hexane ML distillation 0.32kg.

Reaction

Carbamate - 1.38 Kg. Sodium Hydroxide flakes-0.581175Kg. Toluene- 10.23283Kg Activated carbon-0.076875Kg. Hydrochloric acid (min.33%) 0.572565 kg. Methanol -0.24354Kg. Hyflo-0.083025Kg. Hexane -0.60885kg. Water-10.24kg.


Material isolation

Output-1.08 Kg

Product: Paroxetine Stage-V

CO2 (Scrubber)

Aqueous - NA Recovered IPA 98%

Residue after IPA recovery-0.08kg.

Reaction

Crude Paroxetine - 1.08 Kg. Isopropanol-5.92Kg.


Material isolation

Output-1.0 Kg

Product: - Lithium carbonate


2 LiCl + Na2CO

3Li

2CO

3 + 2 NaCl

Water

Material Balance

Materials Input in

Kg Materials Out put in

Kg

Lithium chloride 1.54 Lithium carbonate 1.00

Sodium carbonate anhydrous 1.92 Aq. Layer contain

Water 20.38 water 19.46


Lithium chloride 0.34

Vacuum loss of water 0.9228




Sodium carbonate anhydrous 1.92 kg

Water 20.38 kg

water 19.455 kg



Vacuum loss of water 0.9 kg

out put

1 kg

Reaction

Filter

Product: - Valacyclovir hydrochloride


N

NH

NH2

O

N

N

O

OH OH

O

NH

O

OO

NH

OO

NNH

O

NH2

NN

O

O

Acyclovir Cbz-L-ValineDMF

Stage-I

Stage-III

Crystall ization

H2/Pd-C

MeOH, HCl

+

Cbz-Valacyclovir

O

NH2

N

NH

O

NH2

N

N

O

O

Valacyclovir HCl (Crude)

HClEtOH-Water

Stage-II

Valacyclovir HCl Hydrate

Dicyclohexylcarbodiimide (DCC)

Dimethyl amino pyridine (DMAP)

Material Balance

Stage-I

Input Kg Out put Kg

Acyclovir 1.3621 Stage-I intermediate 1.81159

Cbz-L-valacyclovir 1.89332 Recovered DMF 11.5295

DCC 2.88765 Di-cyclohexyl urea 2.50626

DMF 11.646 Aq. Layer contains

DMAP 0.10897 1) Water 26.9015

Water 29.217 2) DMAP 0.10897

Acetone 29.7346 3) DMF 0.11646

Methanol 7.54603 4) Dicyclohexyl urea 0.64019

Recovered acetone 28.2479

Recovered methanol 7.16873

Residues after acetone recovery containing

1) Chirally impure Stage-I intermediate 0.85812

2) Dicyclohexyl urea 0.64019

3) Water 2.22022

Residues after methanol recovery containing

1) Stage-I intermediate 0.09535

2) Dicyclohexyl urea -

Solvent loss during recovery and drying 1.55279

Total 84.40

84.40

Stage-II

Stage-I intermediate 1.81159 Crude Valacyclovir 1.08696

Methanol 21.5217 Carbon dioxide 0.16304

Hydrochloric acid 0.41667 Toluene 0.36232

Palladium carbon 0.36232 Recovered methanol 20.4456

ethanol 8.5326 Recovered ethanol 8.10597

Hyflo 0.72464 Solvent loss during recovery and drying 1.91123

Residue after distillation of ethanol ML (2nd

Crop) 0.38768

Hyflow and Pd/C 0.9058

Total 33.37

33.37

Stage-III Input Kg Out put Kg

Stage-II intermediate 1.08696 Valacyclovir hydrate 1

Ethanol 10.1413 Recovered ethanol 9.63423

Water 3 Residue after ethanol-water recovery

Valacyclovir HCl 0.08696

Water 3

Solvent loss during recovery and drying 0.50652

Total 14.23

14.23


Product: valcyclovir Stage-01

Aqueous Low TDS 63.18L Di-cyclohexyl urea 98% Recovered DMF 98% Recovered acetone 98% Recovered Methanol 98%

Solid waste-NA

Reaction

Acyclovir - 1.3621kg. Cbz-L-valacyclovir -1.89332Kg. DCC - 2.k2.88765g. DMF -11.646Kg. DMAP -0.10897kg. Water -29.217kg. Acetone -29.7346kg. Methanol -7.54603kg.


Material isolation

Output- 1.81159kg.

Product: valcyclovir Stage-II

CO2 (scrubber)

Aqueous NA Toluene 98% Recovered Methanol 98% Recovered Ethanol 98%

Solid waste-NA Residue after distillation of ethanol ML (2nd Crop)-0.38768kg. Hyflow and Pd/C-0.9058kg.

Reaction

Stage-I intermediate- 1.81159kg. Methanol-21.5217Kg. Hydrochloric acid- 41667g. DMF -11.646Kg. Palladium carbon -0.36232kg. Ethanol -8.5326kg. Hyflo -0.72464kg.


Material isolation

Output- 1.08696 kg.

Product: valcyclovir Stage-III

Aqueous Low TDS 3.08696L Recovered Methanol 98% Solid waste-NA

Reaction

Stage-II intermediate- 1.81159kg. Ethanol-10.1413Kg. Water- 3.0kg.


Material isolation

Output- 1.0 kg.

Product: -trans Retinoic acid, 1-hydroxy-3,3-dimethyl-2-butanone ester(G-101)

Route of synthesis

OH

O ClO+ O

O

O

All trans retinoic acid

Cs2CO3/DMF

1-Chloro picolone trans Retinoic acid, 1-hydroxy-3,3-dimethyl-2-butanone ester(G-101)

Material Balance

Input Kg Out put Kg

Trans retinoic acid 0.90 G-101 (Product) 1.00

1-Chloro picolone 0.90 Aq. Layer contain

Cesium carbonate 1.06 1) Water 55.99

DMF 4.43 2) Cesium chloride 0.50

DM Water 55.96 3) Cesium carbonate 0.57

Isopropanol 2.56 4) DMF 4.43

5) 1-Chloro picoline 0.50

Recovered IPA 2.51

IPA loss in distillation 0.05

CO2 Gas liberated 0.07

Residue after IPA recovery 0.20

Total 65.81 65.81


Product: G-101

CO2 (scrubber)

Aqueous high TDS-61.99L. Recovered IPA 98% Solid waste

Residue after IPA recovery -0.20kg.

Reaction

Trans retinoic acid-0.90kg. 1-Chloro Pico lone -0.90kg. Cesium carbonate -1.06kg. DMF - 4.43kg. DM Water -55.96kg. Isopropanol – 2.56 kg.


Material isolation

Output- 1.0 kg.

Product: - Oxybutynin hydrochloride


O

OHOH

cyclohexyl(hydroxy)phenylacetic acid

Br+

2) CH2O; Dimethyl amine

1)Toluene

Toluene

O

O

OHN

Oxybutynin base

O

O

OHN

ClH

Acetone-HCl

Oxybutynin hydrochloride

Stage-1

Stage-2

Material Balance

Stage-1

Material Input in

Kg Material

Output in Kg

Cyclohexyl

(hydroxyl) phenyl

acetic acid

0.69 Oxybutynin base 1.03

Propargyl Bromide 0.35 Recovered toluene 3.79

Formaldehyde 0.09 Scrubber loss

Diethyl amine 0.22 toluene 0.04

Sodium carbonate 0.31 Carbon dioxide 0.06

Toluene 3.83 aq. Layer contains

Water 2.21 Water 2.29

Sodium bromide 0.30

Sodium carbonate 0.16

Residues after solvent recovery 0.02


Stage-2

Material Input in

Kg Material

Output in Kg

Oxybutanin base 1.03 Oxybutynin hydrochloride 1.00

Dry HCl 0.11 Recovered acetone 1.31

Acetone 1.34 Recovered hexane 1.41

n-Hexane 1.44 Scrubber loss

Acetone 0.03

Hexane 0.03

HCl 0.00

Residue after hexane recovery 0.14



Stage-1

Cyclohexyl (hydroxyl) phenyl acetic acid 0.69 kg


Propargyl Bromide 0.35 kg

Toluene 3.83 kg Carbon dioxide 0.1 kg

Toluene vapours 0.04kg

Water 2.21 kg

Water 2.3 kg

Sodium bromide 0.3 kg

Sodium carbonate 0.2kg



Formaldehyde 0.09 kg Reaction

toluene and distillation

Diethyl amine 0.22 kg

OUT PUT

1.03 kg

Reaction

work up and

distillation

Stage-2

Oxybutanin base 1.03 kg

Dry HCl 0.10 kg

Acetone 1.34kg

n-Hexane 1.44 kg acetone vapours 0.027 kg

hcl vapours 0.0003 kg

Recovered acetone 1.31 kg

Hexane vapours 0.028 kg

MLR

Recovered hexane 1.41 kg

Residue after hexane recovery 0.13 kg

out put

1.0 kg

Reaction and

workup

Filter

Product: - Fexofenadine hydrochloride


MeOH; NaBH 4

Toluene

aq. KHCO 3; KIOH2

O

Cl

O

O

NH

+

O

O

O

NOH

OH

O

O

NOH

1) NaOH;Water:Methanol

2) HCl

OH

O

OH

NOHFexofenadine base

MeOH; HCl

OH

O

OH

NOH

ClH Fexofinadine hydrochloride

Material Balance

Stage-I

Input in Kg Output in Kg

Azacyclonol 0.8965 Stage-I intermediate 1.41

Chloro intermediate 1.420056 Recovered toluene 9.23

Potassium bicarbonate 1.420056 Aq. Layer contain

Potassium iodide 0.04742485 1) Water 4.51

Toluene 9.327186 2) Potassium iodide 0.05

Water 4.4825 3) Potassium chloride 0.25

4) Potassium salt of keto intemediate 0.51

5) Potassium bicarbonate 0.92

Solid waste

Residues after toluene revovery 0.41

Scrubber discharge

Carbon dioxide 0.15

Methanol 0.05

Touene vapour loss 0.09


Stage-II


Stage-I intermediate 1.41 Fexo Base 1.17

Sodium borohydride 0.10 Recovered Methanol 20.92

Sodium Hydroxide 0.32 Aq. Layer contain

Methanol 26.62 Water 8.56

Acetic acid 0.39 Boric acid 0.04

Methyl formate 0.71 Sodium acetate 0.53

Water 8.56 Methanol 4.75

Sodium formate 0.81

Scrubber discharge

Methanol 1.33

Hydrogen 0.0040


Stage-III


Fexo base 1.17 Fexo hydrochloride 1.00

Conc. HCl 0.223949729 Recovered Acetone 9.65

Acetone 10.16120348 Scrubber discharge

Acetone 0.51


Water 0.2156

Residues after Acetone mL revovery 0.1748

Total 11.55 11.55


Stage-1

Azacyclonol 0.89 kg

Chloro intermediate 1.42 kg

Potassium bicarbonate 1.42 kg

Potassium iodide 0.047 kg Carbon dioxide 0.15 kg

Toluene 9.32 kg Methanol vapour loss 0.05 kg

Water 4.48 kg Toluene vapour loss 0.09 kg

Water 4.51 kg

MLR Potassium iodide 0.05 kg

Potassium chloride 0.25 kg

Potassium salt of keto intemediate 0.51 kg

Potassium bicarbonate 0.92 kg

Residues after toluene revovery 0.41 kg


out put

1.41 kg

Reaction and

workup

Filter

Stage-2


Sodium borohydride 0.1 kg

Sodium Hydroxide 0.32 kg

Methanol 26.32 kg

Acetic acid 0.39 kg Methanol vapours 1.33 kg

Methyl formate 0.71 kg Hydrogen 0.004 kg

Water 8.56 kg

Recovered Methanol 20.92 kg

Water 8.56 kg

MLR Boric acid 0.04 kg


Methanol 4.75 kg

Sodium formate 0.81 kg

out put

1.17 kg

Reaction and

workup

Filter

Stage-3

Fexo base 1.17 kg

Conc. HCl 0.224 kg

Acetone 10.16 kg Acetone to scrubber 0.51 kg

Hydrochloric acid to scrubber 0.0013 kg

Water vapours 0.22 kg

MLR Recovered Acetone 9.65 kg

Residues after Acetone mL revovery 0.175 kg

out put

1.0 kg

Reaction and

workup

Filter

Product: - Meclizine hydrochloride


+

O

Cl

4-Chloro benzophenone

NaOH, NaBH 4

Methanol-Water

Cl

Cl

CaCl 2-HCl Water N

NH

Cl

Piperazine

Toluene, TBAB

N

NH

Cl

piperazine

1-[(4-chlorophenyl)(phenyl)methyl]

piperazine

(4-chlorophenyl)(phenyl)methanol

(4-chlorophenyl)(phenyl)methanol 1-chloro-4-[chloro(phenyl)methyl]benzene 1-[(4-chlorophenyl)(phenyl)methyl]

OH

Cl

OH

Cl

Cl

Step-1a

Step-1bStep-2

3-methyl benzyl chloride

1) Triethyl amine-Toluene2) HCl N

NCl

ClHMeclizine hydrochloride

Step-3

Material Balance

Step-1a

Material

Input in

Kg Material

Output in

Kg

4-chloro benzophenone 0.91 4-chlorobenzhydrol (Wet) 1.13

Methanol 3.59 Aq. Layer contain


Sodium hydroxide 0.02 Methanol 3.59

Sodium borohydride 0.08 Sodium acetate 0.23

Acetic acid 0.15 Sodium hydroxide 0.01

Boric acid 0.00

4-chlorobenzhydrol 0.06

Hydrogen scrubber

discharge 0.0033


Step-1b

Material

Input in

Kg Material

Output in

Kg

(4-chlorophenyl) (phenyl) methanol 0.92 Toluene layer with intermediate 6.85

Conc. HCl (C. P. grade) 5.90 Aq. Layer contain

Calcium chloride 1.11 Water 11.01

Toluene 5.86 Calcium chloride 1.11

Purified Water 6.81 Hydrochloric acid 1.62


Step-2

Material

Input in

Kg Material

Output in

Kg

1-Chloro-4-[Chloro(phenyl)

methyl]benzene 6.85


methyl]benzene 0.93

Piperazine (anhydrous) 1.30 recovered toluene 8.52

TBAB 0.09 Recovered Hexane 0.71

Toluene 2.74 toluene scrubber loss 0.09

Hexane 0.74 Hexane scrubber loss 0.04

Sodium hydroxide 0.36 Aq. layer containr contain

Purified Water 11.80 Water 11.80

TBAB 0.09


Sodium hydroxide 0.20

Piperazine 0.94



Step-3

Material

Input in

Kg Material

Output in

Kg

1-[(4-Chlorophenyl)(phenyl)

methyl] piperazine 0.93

Pure meclizine

dihydrochloride 1.00

Toluene 16.86 Recovered toluene 16.69

Triethylamine 0.48 Recovered Acetone 12.20

3-Methylbenzylchloride 0.48 Scrubber loss

DM-water 18.52 Toluene scrubber loss 0.17

Anhydrous sodium sulfate 0.37 Acetone scrubber loss 0.25

Hydrochloric acid (CP grade) 0.98 HCl Scrubber loss 0.06

Activated charcoal 0.05 Triethyl amine 0.13

Hyflow 0.05 Water 0.64

Acetone 12.45 Aq. Layer contain

Water 18.52

Triethyl amine hydrochloride 0.47

Solid residues

Sodium sulfate 0.37


Hyflo 0.05

Residue after sovlent recoveries 0.57



Stage-1a

Methanol 3.59 kg

4-chloro benzophenone 0.91 kg

Water 21.79 kg


Sodium borohydride 0.08 kg Hydrogen scrubber discharge 0.0033 kg

Acetic acid 0.15 kg

Water 21.51 kg

Methanol 3.59 kg



Boric acid

4-chlorobenzhydrol 0.06 kg

out put

1.13 kg

Reaction and

workup

Filter

Stage-1b

Conc. HCl (C. P. grade) 5.9 kg

(4-chlorophenyl) (phenyl) methanol 0.92 kg

Calcium chloride 1.11 kg

Toluene 5.86 kg

Purified Water 6.81 kg

Water 11.01 kg



out put

6.85 kg

Reaction and

workup

Filter

Stage-2

Stage-2

Piperazine (anhydrous) 1.13 kg

TBAB 0.09 kg

1-Chloro-4-[Chloro(phenyl) methyl]benzene 6.85 kg


Toluene 2.74 kg

Hexane 0.74 kg


Water 11.8 kg

Sodium hydroxide 0.36 kg Work up TBAB 0.09 kg

and isolation Sodium chloride 0.24 kg


Piperazine 0.94 kg


Recovered Hexane 0.71 kg

Toluene scrubber loss 0.09 kg

out put Hexane scrubber loss 0.04 kg

0.93 kg Residues after solvent recovery 0.35 kg

Reaction and

workup

Filter

Stage-3

Toluene 16.86 kg

1-[(4-Chlorophenyl)(phenyl) methyl] piperazine 0.93

kg

Triethylamine 0.48 kg

3-Methylbenzylchloride 0.48 kg Triethyl amine 0.13 kg

DM-water 18.52 kg

Anhydrous sodium sulfate 0.37 kg Anhydrous sodium sulfate 0.37 kg

Activated charcoal 0.05 kg Activated charcoal 0.05 kg

Hyflow 0.05 kg Hyflow 0.05 kg

Water 18.52 kg

Triethyl amine hydrochloride 0.47 kg

HCl Scrubber loss 0.06 kg

Hydrochloric acid (CP grade) 0.98 kg

Acetone 12.45 kg workup


Acetone scrubber loss 0.25 kg

Water 0.64 kg

MLR


Recovered Acetone 12.2 kg

out put

1.0 kg

Reaction and

workup

Filter

Filter

Product: - Hdroxazine hyrochloride


+

O

Cl

4-Chloro benzophenone

NaOH, NaBH 4

Methanol-Water

Cl

Cl

CaCl 2-HCl Water N

NH

Cl

Piperazine

Toluene, TBAB

N

NH

Cl

piperazine

1-[(4-chlorophenyl)(phenyl)methyl]

piperazine

(4-chlorophenyl)(phenyl)methanol

(4-chlorophenyl)(phenyl)methanol 1-chloro-4-[chloro(phenyl)methyl]benzene 1-[(4-chlorophenyl)(phenyl)methyl]

OH

Cl

OH

Cl

OCl OH

Step-1a

Step-1bStep-2

1) Triethyl amine-Toluene2) HCl-IPA

Step-3

N

N

Cl

O

OHClH

ClH2-(2-chloroethoxy) ethanol

Hydroxazine Dihydrochloride

Material Balance

Step-1a

Material

Input in

Kg Material

Output in

Kg

4-chloro benzophenone 1.46 4-chlorobenzhydrol (Wet) 1.83

Methanol 5.79 Aq. Layer contain


Sodium hydroxide 0.04 Methanol 5.79

Sodium borohydride 0.13 Sodium acetate 0.37

Acetic acid 0.25 Sodium hydroxide 0.02

Boric acid 0.01

4-chlorobenzhydrol 0.09

Hydrogen scrubber

discharge 0.01


Step-1b

Material

Input in

Kg Material

Output in

Kg

(4-chlorophenyl)

(phenyl) methano 1.48

Toluene layer with

intermediate 11.05

Conc. HCl (C. P. grade) 9.51 Aq. Layer contain

Calcium chloride 1.79 Water 17.75

Toluene 9.45 Calcium chloride 1.79

Purified Water 10.97 Hydrochloric acid 2.61


Step-2

Material Input

in Kg Material

Output

in Kg


methyl]benzene 11.05

1-[(4-Chlorophenyl)

(phenyl) methyl] piperazine

hydrochloride

1.49

Piperazine (anhydrous) 2.09 recovered toluene 13.73

TBAB 0.15 Recovered Hexane 1.14

Toluene 4.42 toluene scrubber loss 0.14

Hexane 1.20 Hexane scrubber loss 0.06

Sodium hydroxide 0.59 Aq. layer containr contain

Purified Water 19.02 Water 19.02

TBAB 0.15



Piperazine 1.51

Residues after solvent

recovery 0.56


Step-3

Material

Input

in Kg Material

Output

in Kg

1-[(4-Chlorophenyl)(phenyl)

methyl]piperazine 1.49 Hydroxazine Di HCl 1.00


Triethylamine 1.21 Recovered IPA 9.75

2-chloroethoxy ethanol 0.91 Scrubber loss

Water 29.10 Toluene scrubber loss 0.06

Anhydrous sodium sulfate 0.37 IPA Scrubber loss 0.10

IPA-HCl 15% 2.61 Triethyl amine 0.47

Activated charcoal 0.07 Aq. Layer contain

Hyflow 0.07 Water 29.10

IPA 7.63 Triethyl amine

hydrochloride 1.00

Sodium chloride 0.60 Sodium chloride 0.60

2-chloro ethoxy ethanol 0.26

Solid residues

Sodium sulfate 0.37


Hyflo 0.07

Residue after solvent

recoveries 1.27



Stage-1a

4-chloro benzophenone 1.46 kg

Methanol 5.79 kg

Water 35.12 kg

Sodium hydroxide 0.04 kg Hydrogen scrubber discharge 0.01 kg

Sodium borohydride 0.13 kg

Acetic acid 0.25 kg

Water 34.67 kg

Methanol 34.67 kg



Boric acid 0.01 kg

4-chlorobenzhydrol 0.09 kg

out put

1.48 kg

Filter

Reaction and

workup

Stage-1b

(4-chlorophenyl) (phenyl) methano 1.48 kg

Conc. HCl (C. P. grade) 9.51 kg


Toluene 9.45 kg


Water 17.75 kg



out put

11.05 kg

Reaction and

workup

Filter

Stage-2

1-Chloro-4-[Chloro(phenyl) methyl]benzene 11.05 kg

Piperazine (anhydrous) 2.09 kg

TBAB 0.15 kg

Toluene 4.42 kg

Hexane 1.2 kg


Water 19.02 kg

Sodium hydroxide 0.59 kg Work up TBAB 0.15 kg

and isolation Sodium chloride 0.39 kg


Piperazine 1.51 kg

recovered toluene 13.73 kg


toluene scrubber loss 0.14 kg

out put Hexane scrubber loss 0.06 kg

1.49 kg Residues after solvent recovery 0.56 kg

Reaction and

workup

Filter

Stage-3

1-[(4-Chlorophenyl)(phenyl) methyl]piperazine 1.49 kg

Toluene 5.82 kg

Triethylamine 1.21 kg

2-chloroethoxy ethanol 0.91 kg

Water 29.1 kg Triethyl amine 0.47 kg


Activated charcoal 0.07 kg Sodium sulfate 0.37 kg

Hyflow 0.07 kg Activated carbon 0.07 kg

Anhydrous sodium sulfate 0.37 kg Hyflo 0.07 kg

Water 29.1 kg

Triethyl amine hydrochloride 1 kg


2-chloro ethoxy ethanol 0.26 kg

IPA-HCl 15% 2.61 kg

IPA 7.63 kg workup


IPA Scrubber loss 0.1 kg

Water 0.64 kg

MLR


Recovered IPA 9.75 kg

Residue after sovlent recoveries 1.27 kg

out put

1.0 kg

Filter

Reaction and

workup

Filter

Product: - Fluconazole


FF

FF

O

ClF

F

O

N+

NN

NH2

Cl-

FF

O

N

N

NF

F

NN

NO

N

NN

F

FN

+N

N

OH

NH2

N

NN NH2

Methane sulfonicacid; Isopropanol

Stage-II

Stage-IIIStage-IV(a)

NaNO 2-HCl

NaNO 2-HCl

AlCl3-MDC

Acetonitrile

N

NN NH2

MDC/KOH

I-

S+

O

1,3-Difluorobenzene 2-chloro-1-(2,4-difluorophenyl)ethanone4-amino-1-[2-(2,4-difluorophenyl)-2-oxoethyl]-4H-

1,2,4-triazol-1-ium Chloride

1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone

1-{[2-(2,4-difluorophenyl)oxiran-2-yl]methyl}-1H-1,2,4-triazole

4-amino-1-[2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl]-1H-1,2,4-triazol-4-ium

methane sulphonate

SO

O

CH3

OH

N

NN

F

FN

N

N

OH

Chloroacetyl chloride

Fluconazole

Material Balance

Stage-I

Name Input in Kg Name

Output in Kg

1,3-Difluorobenzene 0.89 Stage-I intermediate 1.92

Chloro acetyl chloride (98%)

0.90 Recovered dichloromethane 6.77

Aluminium trichloride 1.04 Recovered Acetonitrile 4.19

Dichloromethane 7.13 Scrubber loss

Conc. HCl 2.67 Vacuum loss MDC 0.36

Water 12.14 Vacuum loss Acetonitrile 0.04

5% Brine 0.89 Aq layer containing

4-amino-1,2,4-triazole 0.69 Water 14.44

Acetonitrile 4.23 Sodium choride 0.04

Dissolved HCl 1.66

Scrubber HCl 0.29

Alumniium hydroxide 0.61

Chloriacetic acid 0.25

Residues after Acetonitrile recovery 0.02


Stage-II


Output in Kg


Sodium Nitrite 0.50 Scrubber discharge

Hydrochloric acid (30%) 1.44 Nitrogen 0.20

25% Aq. Ammonia 1.18 Aq. Layer containing


Ammonium chloride 0.62

Sodium choride 0.42

Ammonia 0.10

Stage-II intermediate taces 0.13

Solid residues -


Stage-III


Output in Kg

Stage-II intermediate 1.42 Epoxide 1.43

Trimethylsulfoxonium

iodide 1.425213

Recovered MDC 27.37

Potassium hydroxide 1.676613 Recovered Hexane 2.42

Citrimide 0.0053851 Scrubber Loss

Dichoromethane 28.810362 MDC Loss to scrubber 1.44

Hexane 2.5448917 Hexane Loss to scrubber 0.13

Water 23.405691 Dimethyl sulfide 0.40

Aq. Layer containing

Water 23.66

Potassium iodide 1.08

Citrimide 0.01

Potassium hydroxide 1.26

Residues after Hexane ML recovery 0.10


Stage-IV


Output in Kg

Epoxide 1.43 Crude fluconazole 1.21

4-amino-1,2,4-triazole 0.9875111 Recovered IPA 4.46

Methane sulfonic acid 0.659722 Recovered MDC 43.33

Isopropanol 4.5096008 Recovered toluene 8.86

Sodium Nitrite 1.0788177 Ethyl acetate 2.54

Conc. HCl 3.9437574 Scrubber Discharge

25% ammonium

hydroxide 4.143803

IPA 0.05

Toluene 8.9527579 MDC 2.28

Ethyl acetate 2.5634423 Toluene 0.09

Dichoromethane 45.610411 Ethyl acetate 0.03

Water 30.01 Nitrogen 0.33

Aq. Layer containing

Water 35.88


Ammonium methane sulfonate 0.78


Dissolved ammonai 1.93

Residues after solvent recoveries 0.19


Stage-V


Output in Kg

Crude fluconazole 1.21 Pure fluconazole 1.00

Acetone 0.4323844 Scrubber loss

Ethyl acetate 0.3813728 Water 0.22

Activated carbon 0.0607281 Aq. Layer contain

Hyflo 0.1214563 Water 28.92

Water 29.15 Acetone 0.43

Ethyl acetate 0.38

Product 0.21

Solid residues

Hyflo 0.12

Carbon 0.06



Stage-1

1,3-Difluorobenzene 0.89 kg

Dichloromethane 7.125 kg

Aluminium trichloride 1.043 kg Reaction

Chloro acetyl chloride (98%) 0.90 kg

Conc. HCl 2.67 kg Water 14.44 kg

Water 12.14 kg Workup Sodium choride 0.04 kg

5% Brine 0.89 kg Dissolved HCl 1.66 kg

Scrubber HCl 0.29 kg

Alumniium hydroxide 0.61 kg

Chloroacetic acid 0.25 kg

Distillation

Recovered dichloromethane 6.77 kg

Acetonitrile 4.23 kg

4-amino-1,2,4-triazole 0.69 kg Reaction

Recovered Acetonitrile 4.19 kg

Vacuum loss Acetonitrile 0.04 kg

Residues after Acetonitrile recovery 0.02 kg

Out put

1.92 kg

Stage-2

Nitrogen 0.19 kg

Water 13.7 kg


Hydrochloric acid (30%) 1.44 kg Reaction

Sodium Nitrite 0.49 kg

25% Aq. Ammonia 1.175 kg

Filter

Water 15.89 kg

Ammonium chloride 0.622 kg

Sodium choride 0.42 kg

out put Ammonia 0.09 kg

1.42 kg Stage-II intermediate taces 0.13 kg

Stage-3

Potassium hydroxide 1.68 kg

Water 23.4 kg

Dichoromethane 28.81 kg

Trimethylsulfoxonium iodide 1.425 kg reaction

Citrimide 0.005 kg


MDC Loss to scrubber 1.44 kg

Hexane Loss to scrubber 0.13 kg

Dimethyl sulfide 0.4 kg

Hexane 2.54 kg distillation



Filter

Water 23.66 kg

Potassium iodide 1.075 kg

Citrimide 0.005 kg

out put Potassium hydroxide 1.26 kg

1.43 kg Residues after Hexane ML recovery 0.104 kg

Stage-4

Isopropanol 4.509 kg

Epoxide 1.43 kg

4-amino-1,2,4-triazole 0.99 kg Reaction

Methane sulfonic acid 0.66 kg

IPA 0.045 kg

Water 30.0 kg Distillation

Recovered IPA 4.46 kg

Conc. HCl 3.943 kg

Sodium Nitrite 1.08 kg workup


filter

MDC 2.28 kg

Toluene 0.089 kg

Water 35.87 kg

Dichoromethane 45.61 kg Workup & Sodium chloride 0.91 kg

25% ammonium hydroxide 4.14 kg distillation Ammonium methane sulfonate 0.776 kg

Toluene 8.95 kg Ammonium chloride 1.02 kg

Dissolved ammonai 1.9 kg



filter

out put

1.21 kg

Stage-5

Water 29.14 kg

Acetone 0.43 kg Reaction


Crude fluconazole 1.21 kg

Filter

Hyflo 0.121 kg

Activated carbon 0.06 kg reactor Carbon 0.06 kg

Hyflo 0.121 kg

filter Water 28.92 kg

Acetone 0.43 kg


Product 0.21 kg

Water 0.22 kg

out put

1.0 kg

Product: - Colestipol hydrochloride


NH2

NHNH2

O

Cl

+Diethylene triamine

OHNH

NH

N

NH

NH

N

NH

OH

OH

NH

N

NH

OH

OH

NH

Epichlorohydrine

Sodium dodecylbenzene sulfonate

NaOH/Toluene Colestipol

Material Balance:-

Input Output

Name qty in Kg Name qty in Kg

Diethylenetriamine 0.5 Colestipol 1.00

Epichlorohydrin 0.901333 Recovered toluene 4.29165

Sodium Dodecyl benzene Sulphonate 0.006833 Aq. Layer containing

50% Caustic lye 0.658667 Water 30.57933

Toluene 4.335 Sodium hydroxide 0.329333

Water 33.25 Sodium dodecyl benzene sulfonate 0.006833

Epichlorohydrin 0.14205

Diethylene triamine 0.256069

Vacuum loss

Toluene 0.04335

Water 3

Residues after toluene recovery 0.0032



Diethylenetriamine 0.5 kg


Sodium Dodecyl benzene Sulphonate 0.0068 kg Toluene 0.043 kg

50% Caustic lye 0.67 kg Water 3.0 kg

Toluene 4.33 kg

Water 33.25 kg


Water 30.58 kg

MLR Sodium hydroxide 0.33 kg

Sodium dodecyl benzene sulfonate 0.0068 kg


Diethylene triamine 0.26 kg

Residues after toluene recovery 0.03 kg

out put

1.0 kg

Reaction

Filter

Product: - Esomeprazole magnesium


O

NH

NS N

O

O

NH

NS N

O

O

O

NH

NS

O

O Mg

K+

O

NH

NS

O

O

OH2OH2 OH21) Water / MgSO

4

1) Cumine hydroperoxideTitanium isopropoxideDiethyl-L-TartarateToluene; Di-isopropyl ethyl amine; 2) KOH

2) MeOH-Acetone

Esomeprazole Magnesiumtrihydrate

Material Balance:-

Stage-I

Name Input in

Kg Name O/p in

Kg

Omeprazole sulfide 1.29 Crude esomeprazole 1.17

Cumene hydroperoxide 0.7998 Recovered toluene 28.79

Diethyl tartarate (D) 0.4902 Recovered methanol 0.88

Titanium isopropoxide 0.3354 Aq. Layer containing

Toluene 29.07918 Water 30.63

water 33.54 Potassium sulfate 0.88

Di-isopropyl ethyl amine 0.148608 Titanium hydroxide 0.14

Potassium hydroxide 0.284832 tartaric acid 0.36

Magnesium Sulphate Heptahydrate 0.7224 Ethanol 0.22

Methanol 0.9288 Di-isopropyl ethyl amine 0.15

Isopropanol 0.28

impure esopeprazole 0.21

Scrubber loss

Toluene 0.29

Methanol 0.05

Water 2.94

Residue containing

Cumine 0.63


Stage-II

Name Input in

Kg Name O/p in

Kg

Crude esomeprazole 1.17 Pure esomeprazole 1.00

Methanol 8.22 Recovered methanol 7.81

Activated carbon 0.01 recovred acetone 6.69

Acetone 7.04 Solid residues

Hyflo 0.06 Carbon 0.01

Hyflo 0.06


Vacuum loss

Methanol 0.41

Acetone 0.35



Stage-1

water 33.54 kg

Diethyl tartarate (D) 0.49 kg

Titanium isopropoxide 0.335 kg

Omeprazole sulfide 1.29 kg

Toluene 29.079 kg

Di-isopropyl ethyl amine 0.149 kg

Cumene hydroperoxide 0.7998 kg

Potassium hydroxide 0.28 kg Toluene vapours 0.29 kg

Magnesium Sulphate Heptahydrate 0.72 kg Methanol vapours 0.05 kg

Methanol 0.929 kg Water vapours 2.94 kg



Water 30.63 kg

Potassium sulfate 0.88 kg

MLR Titanium hydroxide 0.14 kg

tartaric acid 0.36 kg

Ethanol 0.22 kg

Di-isopropyl ethyl amine 0.15 kg

Isopropanol 0.28 kg

impure esopeprazole 0.21 kg

residue containing Cumine 0.63 kg

out put

1.17 kg

Reaction and

work up

Filter

Stage-2

Crude esomeprazole 1.17 kg

Methanol 8.217 kg Methanol vapours 0.41 kg

Acetone 7.04 kg Acetone vapours 0.35 kg

Reaction


recovred acetone 6.69 kg

Activated carbon 0.011 kg Carbon 0.01 kg



Out put

1.0 kg

Product: - Metformin hydrochloride


NH

NH NH2

NC + NH3C CH3

HClH N

H

NH2

NHNH

NMix xylene

Purified water ClH

Dicyanodiamide Dimethylamine hydrochlorideMetformin hydrochloride

Molecular formula: C2H4N4Molecular formula: C2H8ClN Molecular formula: C4H12ClN5

Molecular weight: 84.08 Molecular weight: 81.54 Molecular weight: 165.62

CharcoalMethanol

Material Balance

Material Input in


Kg

DCDC 0.56 Metformin 1.00

DMA-HCl 0.66 Recovered methanol 0.40

Mixed Xylene 1.07 Recovered Xylene 1.02

Methanol 0.45 Rec. water 1.52

Activated Carbon 0.00 Methanol vacuum loss 0.05

Hyflo 0.00 Xylene vacuum loss 0.04

Water 1.31

Solid waste

Carbon 0.00

Hyflo 0.00




DCDC 0.56 kg

DMA-HCl 0.66 kg

Mixed Xylene 1.067 kg

Water 1.312 kg

Activated Carbon 0.004 kg Carbon 0.004 kg

Hyflo 0.003 kg Hyflo 0.0032 kg

Methanol vacuum loss 0.048 kg

Xylene vacuum loss 0.0424 kg

Distillation


Recovered Xylene 1.0248 kg

distilled water 1.524 kg

filter


out put

1 kg

Reaction and

workup

Filter

Product: - Sucralfate


OH

O

OH

OHOH

O

O

OH

OH

OH

OH

Sucrose

1) Chlorosulfoic acid2) Ammonia

2-Picoline

Sucrose Octaammonium sulfonate salt

S

O

O

O

S

O

O

O

SO

O

OS

O

O

O

O

O

O

O

O

O

O

O

O

S

O

O

O

O

S

O

O O

O

SOO

O

S

O

O

O

Al-

O+

O+

Al-

O+ O

+

Al-

O+

O+Al

-

O+

O+

Al-O

+

O+

Al-O

+

O+

Al-

O+

O+

Al-

O+

O+

Al-

OH

OH

Al-

OHOH

Al-

OH

OH

Al-OH

OH

Al-

OHOH

Al-

OH

OH

Al-

OH

OH

Al-

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

AlOH OH

Cl

Sucralfate

S

O

O

OH

SO

O

OH

SO

OOH

SO

O OH

O

O

O

O

O

O

OO

O

S

O

OO

OH

SOO

OOH

SO

OOH

SO

O

OH

8NH3

Material Balance

Stage-1

Input Quantity

in Kg Out put

Quantity

in Kg

Sucrose 0.23 Sucrose octanesulfate ammonium salt 0.67

Chlorosulfonica acid 0.63 Recovered methanol 4.97

2-Picoline 1.97 Recovered picoline 1.95

Aq. Ammonia 25% 0.82 Water recovered 0.61

Methanol 5.07 Scrubber loss

Water 1.89 Methanol 0.10

Hyflo 0.05 Picoline 0.02

Charcoal 0.02 Water recovered 0.01

Ammonia 0.02

Residues contains


Ammonium sulfate 0.02

Activated crobon 0.02

Hyflo 0.05

Aq. Layer contains

Water 1.89

Sucrose octanesulfate ammonium salt 0.07


Stage-2

Sucrose octasulfate ammonium salt 0.67 Sucralfate 1.00

Aluminium chlorohydrate 0.97 Recovered ethanol 5.96

ethanol 6.08 Recovered methanol 6.24

Methanol 6.37 Water 3.74

Water 3.74 Scrubber loss

Ethanol 0.12

Methanol 0.13

Water 0.09

Residues after revovery


Aluminium chlorohydrate 0.04

Product 0.24



Stage-1

2-Picoline 1.97 Kg

Chorosulfonic acid 0.63 Kg

Sucrose 0.23 Kg Rec water 0.61 kg

25% Aq. Ammonia 0.82 Kg Recovered methanol 4.97 Kg

Methanol 0.79 Kg Recovered picoline 1.95 Kg

Methanol scrubber loss 0.1 Kg

Picolin scrubbr loss 0.02 Kg

Ammonia scrubber loss 0.02

Recovery of

Mother Liquor

Methanol washing 0.68 Kg

Crude stage-I

Water 1.42 Kg

Activated carbon 0.023 Kg

Hyflo 0.045 Kg

Methanol 2.25 kg

Residues

Ammonium chloride 0.28 Kg

Ammonium sulfate 0.02 Kg

Aq. layer contain

Water wash 0.47 Kg Water 1.89

Stage-I intermediate 0.07

Solid residues Methanol wash 1.35 Kg

Hyflo 0.05 Kg

Chrocoal 0.02 Kg

Reactor

Centrifuge

Reactor

Centrifuge &

Drying

Filtration

Reactor

Filtration

Stage-I intermediate 0.67 Kg

Stage-2

Water 3.74 Kg

Alumnium chlorohydrate 0.97 Kg

Stage-I:- 0.67 Kg

Ethanol 6.08 Kg

Methanol 3.63 Kg

Decanted aq. layer

Methanol wash 2.74 Kg

Sucralfate 1 Kg

Recovered ethanol 5.96 Kg

Recovered methanol 5.2 Kg

Recovered Water 3.74

Ethanol Scruber loss 0.12 Kg

Methanol scruber loss 0.11 Kg

Water scruber loss 0.08 Kg

Residues

Ammonium chloride 0.26 Kg

Aluminium chlorohydrate 0.04 Kg

Product 0.24 kg

Recovery reactor

Reactor

Centrifuge and drying

Product: -Ractopamine hydrochloride


1) NH3

2) H2,Pd/C Methanol

3) HCl

Raspberry KetoneOctopamine Hydrochloride

ClHNH2

OH

OH O

OH

+

HydrochlorideRactopamine

ClH

NH

OH

OH

OH

Material Balance

Input Kg Out put Kg

Octopamine HCl 0.87 Racto HCl 1.00

Mathanol 8.79 Recovered methanol-1 8.35

Ammonia 0.09 Recovered methanol-2 6.78

Activated carbon 0.04 Recovered Ethyl acetate 9.16

Mathanol 7.14 Vaccum loss of Methanol 0.80

Raspberry ketone 0.90 Vaccum loss of ethyl acetate 0.19

Catalyst 0.08 Solid Waste

water wash 2.78 Activated carbon 0.04

Water 6.72 Residue contain RK 0.17

Ethyl acetate 9.34 Aq. Effluent contains

1) Water 9.62

2) Amminium chloride 0.29

3) Octopamine 0.03

4)Ractopamine 0.33

Total 36.76 36.76

Aqueous high TDS-10.28L. Recovered Methanol 98% Recovered Methanol 98% Recovered Ethyl Acetate-98%

Solid waste Activated carbon-0.04kg. Residue contain RK -0.17kg. .

Reaction

Octopamine HCl – 0.87kg. Methanol-8.89Kg. Ammonia – 0.09g. Activated carbon -0.04Kg. Methanol -7.14kg. Raspberry ketone -0.90kg. Catalyst -0.08kg. Water wash-2.78kg. Water-6.72kg. Ethyl acetate-9.34kg.


Material isolation

Output- 1.0 kg.

Product: - Benzocaine


N+

O-

O

OHO

H2SO4

Ethanol

N+

O-

O

OO

NH2

OO

H2/Pd - C

Toluene

4-nitrobenzoic acid ethyl 4-nitrobenzoate Benzocaine

Material Balance

Stage-I

Input Kg Out put Kg

PNBA 1.47 Ester 1.50

Ethanol 1.74 Aq. Layer

Sulfuric acid 0.68 1) Water 13.41

Sodium carbonate 0.09 2) SodiumSulfate 0.12

Water 13.24 3) Sulfuric acid 0.59

Hyflo 0.00 4) Ethanol 1.34

5) Ester 0.22

Hyflo 0.00

Carbon dioxide 0.04

Total 17.21 17.21

Stage-II

Stage-I 1.50 Stage-II 1.00


Pd/C 0.00 Vacuum loss toluene 0.03

Sodium bicarbonate 0.00 Pd/C 0.00

Hyflo 0.00 Aq. Layer

Hydrogen consumed 0.05 1) Water 0.28

Solid waste

Hyflo 0.00

Sodium carbonate 0.00

Residue after toluene distillation 0.27

Total 4.63 4.63


Product: Benzocaine Stage-01

CO2 (Scrubber)

Aqueous high TDS-15.68L. Ethanol 98% Solid waste -NA

Reaction

PNBA–1.47kg. Ethanol-1.74kg. Sulfuric acid – 0.68kg. Sodium carbonate-0.09Kg. Water -13.24kg.


Material isolation

Output- 1.50 kg.

Product: Benzocaine Stage-II

Aqueous Low TDS-0.28L. Recovered Toluene 98% Solid waste Residue after toluene distillation 0.27kg.

Reaction

Stage-I– 1.50kg. Toluene- 3.08kg. Hydrogen consumed– 0.05kg.


Material isolation

Output- 1.0 kg.

Documents

€¦ · · 2016-12-31... (2-nitrophenyl) disulfide 2-Nitro benzene sulfanyl chloride Cl 2 Gas Material Balance Step-1 ... Chlorine gas 0.32 Recovered hexane 2.34 ... Material Balance