MBG-1,2,3,4 All PFD

CUSTOM PHARMACEUTICAL
PHARMACEUTICALSERVICES
SERVICES
ISMS Class:Internal
ISMS Class: Restricted
PROCESS FLOW DIAGRAM CMBG-1
ISMS Version:1.0
CMPG-4 CMBG-1
Batch size 40.00 Kg Out put Weight in Kg 48.61 Kg

Mol. Wt 311.00 Mol. Wt 429.50
Moles 0.1286 Moles 0.1132
Yield W/W 1.21
Yield (%) 88.00 Scale Up ratio 400
Lab Batch Plant Batch

Mole
Sr. No. Raw material M. wt Moles W/W V/W Density
Ratio
Qty. (gm) Vol. (ml) Qty. (Kg) Vol. (L)
1 CMPG4 100 40.00 … 311.00 0.129 1 … 1 …

4-Methoxybenzaldehyde
2 85.6 80 34.24 32.0 182 … 1.2 0.86 0.8 1.07
dimethylacetal
3 Camphorsulphonic acid Lot-1 2.4 … 0.96 … 232 … 0.03 0.024 … …
4 Camphorsulphonic acid Lot-2 … … … … … … … … … …
5 Dimethyl formamide … 300 … 120.0 … … … … 3.0 …
6 Acetonitrile … 100 … 40.0 … … … … 1.0 …
7 Triethylamine … 40 … 16.0 … … … … 0.4 0.72
8 DM water Lot-1 … 600 … 240.0 … … … … 6.0 …
9 DM water Lot-2 … 200 … 80.0 … … … … 2.0 …
10 n-Hexane Lot-1 … 400 … 160.0 … … … … 4.0 …
11 n-Hexane Lot-2 … 300 … 120.0 … … … … 3.0 …
12 n-Hexane Lot-3 … 300 … 120.0 … … … … 3.0 …
13 n-Hexane Lot-4 … 200 … 80.0 … … … … 2.0 …
* Camphor sulphonic acid lot-2 is variable quantity
Time
Min. Max.
Vol. Vol.
Cycle
Hr.
120.0 Dimethyl formamide 160 160 1.0

Charge Dimethyl formamide into
40.0 CMPG4 the reactor followed by CMPG-4 at
27.5 ± 2.5°C under N2 atmosphere.
40.0 Acetonitrile Charge Acetonitrile into the reactor 160 200 0.3
at 27.5 ± 2.5°C.
Charge Camphorsulphonic acid

0.96 Camphorsulphonic acid Lot-1 200 200 0.3
Lot-1 into the reactor at
27.5 ± 2.5°C.
Raise the reaction mass 200 200 1.0

temperature to 65 ± 5°C under N2
atmosphere.
Slowly add 4-
Methoxybenzaldehyde dimethyl
acetal into the reactor at 65 ± 5°C
over a period of 30 minutes with
32.0 4-Methoxybenzaldehyde simultaneous distillation of by 200 232 1.0
dimethylacetal product Methanol along with
acetonitrile U/vacuum of 400-450
mmHg.
After addition, distill the by

product Methanol along with 232 232 1.0
Acetonitrile from the reaction mass
under vacuum of NLT 650 mmHg.
Maintain the reaction mass at 65 ± 232 232 5.0

5°C for 3-5 hours under vacuum of
NLT 650 mmHg with continuous
distillation of by product.
Send sample to QC for TLC as CMPG-4 Content 232 232 1.0

CMBG1-01. NMT-5.0%
If complies
If TLC does not comply, maintain 232 232 1.0

the reaction mass at
65 ± 5°C under vacuum with
continuous distillation of by
product till TLC complies.
Cool the reaction mass to 22.5 ± 232 232 1.0

2.5°C.
F-PE-004/00-03.07.2009 Page 1 of 15
SERVICES
ISMS Class:Internal
ISMS Version:1.0
16.0 Triethylamine Charge Triethyl amine into the

reactor at 22.5 ± 2.5°C. 232 232 0.5
240.0 DM water Lot-1 232 632 1.0

Reaction mass at 22.5 ± 2.5°C.
160.0 n-Hexane Lot-1
Stir the reaction mass for 15 632 632 0.3

minutes at 30 ± 5°C.
AQ+ Hex
ML
Filter the reaction mass through 576.0 5.0
Centrifuge.
Aq MLs
Wash the material with DM water
80.0 DM water Lot-2 80.0 1.0
Lot-2.
120.0 n-Hexane Lot-2 Slurry wash the material with n-

Hexane Lot-2. 120 120 1.0
Hex MLs
Centrifuge.
120.0 n-Hexane Lot-3 Slurry wash the material with n- 120 120 1.0
Hexane Lot-3.
Hex MLs
Centrifuge.
80.0 n-Hexane Lot-4 Spry Wash the material with n- 1.0

Hexane Lot-4.
Hex MLs
Spin dry the wet materila till no 80.00 1.0
ML comes out of the centrifuse
F-PE-004/00-03.07.2009 Page 2 of 15
SERVICES
ISMS Class:Internal
ISMS Version:1.0
Unload the wet cake into the clean

poly bags
Load the wet material into the 2.0

Vacuum tray drier.
Dry the wet material under vacuum

of NLT 550 mmHg at 3.0
30 ± 5°C for 2-3 hours.
Unload the semi dried material into 1.0

the clean poly bags
Load the semi dried material into 2.0

the tray drier.
Raise the temperature to 67.5 ± 1.0

2.5°C.
Dry the material at 67.5 ± 2.5°C for 15.0

12-15 hours.
Send sample to QC (NMT-1.0%)

for LOD (NMT-1.0%) and Water 4.0
content as CMBG1-02.
If LOD and Water content does not 4.0

comply, dry the material at 67.5 ±
2.5°C till LOD& Water content are
within the limit.
If complies with limit unload the

maerial and Send the sample for
complete analysis
Totral Time Required for this stage, Hrs 58.3
No. of Days 2.43
Total Org.Effluent 320.00 Lt

Total Aq.Effluent 656.0 Lt
Agitator Time
Tag Capacity Max
Sr.No Equipment Detail MOC Type / Min vol Cycle Remarks
No. L/Size/Kg vol
RPM hr
Reaction, Work
1 GLR GLR 1000 SS 316 PBT 120 632 24.3
up and distillation
2 Centrifuse SS 100 L SS 316 … … … 12.0 Product Filtration
3 TD SS SS 317 … … … 32.0 Product drying
F-PE-004/00-03.07.2009 Page 3 of 15
SERVICES
ISMS Class:Internal
ISMS Version:1.0
CMBG-1 CMBG-2

Mol. Wt 429.50 Mol. Wt 550.00
Yield W/W) 1.04

Mole
Ratio
1 CMBG1 100 48.61 … 429.50 0.113 1 … 1.00 …

2 4-Methoxybezyl chloride 72.70 63 35.34 30.63 156.600 0.226 2 0.73 0.63 1.154
3 Sodium hydroxide flakes 46.5 22.60 … 40 0.566 5 0.47 … …
4 Toluene Lot-1 … 1000 … 486.12 … … … … 10.00 …
5 NMP … 200 … 97.22 … … … … 2.00 …
Tetra butyl ammonium
6 1.8 0.88 … 322 … 0.025 … …
bromide(TBAB) 1000 0.018
7 Toluene Lot-2 … 1000 … 486.12 … … … … *** …
8 Hyflow *** … *** … … … *** … …
9 Toluene Lot-3 … 500 … 243.06 … … … … 5.00 …
10 DM water Lot-1 … 800 … 388.90 … … … … 8.00 …
11 DM water Lot-2 … 800 … 388.90 … … … … 8.00 …
12 DM water Lot-3 … 800 … 388.90 … … … … 8.00 …
13 Sodium chloride 250 … 121.53 … … … … 2.50 … …
14 Hexane Lot-1 … 2000 … 972.24 … … … … 20.00 …
15 Hexane Lot-2 … 500 … 243.06 … … … … 5.00 …
Time
Min. Max.
Vol. Vol. Cycle
Hr.
486.1 Toluene Lot-1 Charge Toluene Lot-1 into the reactor 486 493 1.0
followed by NaOH flakes at 27.5 ±
22.6 Sodium hydroxide flakes 2.5°C under N2 atmosphere
Cool the reaction mass to 2.5 ± 2.5°C 1.00
48.6 CMBG1 Charge CMBG1 into the reactor at 2.5 493 507 0.25
± 2.5°C for 15-20 minutes under N2
atmosphere.
Charge NMP into the reactor at 2.5 ±

97.2 NMP 507 605 0.5
2.5°C for 15-20 minutes under N2
atmosphere
Stir the reaction mass at 2.5 ± 2.5°C 0.5

for 30 minutes under N2 atmosphere.
Charge Tetra butyl ammonium

Tetra butyl ammonium bromide(TBAB) into the reactor at
0.9 2.5 ± 2.5°C under N2 atmosphere 605 606 1.0
bromide(TBAB)
Slowly add 4-Methoxybezyl chloride 606 636 2.0

drop wise into the reactor at 2.5 ±
30.6 4-Methoxybezyl chloride 2.5°C under N2 atmosphere.
Stir the reaction mass at 2.5 ± 2.5°C

for 20-30 minutes under N2 636 636 0.5
atmosphere.
Raise the reaction mass tempreature 1.0

to 30 ± 5°C under N2 atmosphere.
Maintain the reaction mass at 30 ± 8.0

5°C for 5-8 hours under N2
atmosphere.
Send sample to QC for TLC as CMBG-1 Content 636 636 1.0

CMBG2-01 NMT-5.0%
If complies
If TLC does not comply, maintain the 636 636 2.0

reaction mass at
30 ± 5°C till TLC complies.
*** Hyflow Hyflow Filtration of reaction mass through *** 636 636 3.0
*** Toluene Lot-2 bed nutch filter
F-PE-004/00-03.07.2009 Page 4 of 15
SERVICES
ISMS Class:Internal
ISMS Version:1.0
MLs
Collect the MLs from nutch filter 583.3 0.5
243.06 Toluene Lot-3 Wash the bed with Toluene Lot-3 1.0
MLs
Suck dry the material till no more 243.06 1.0
filtrate observed.
826.4
Charge the total filtrate into the
826 826 0.5
reactor
Wash the oragic layer with DM water

388.9 DM water Lot-1 826 1215 0.5
Lot-1
Stir the reaction mass for 15-30

minutes. 1215 1215 0.5
Settle the reaction mass for 30 1215 1215 0.5

minutes
Aq Layer
Separate bottom aqueous layer and 388.9 826 1215 1.0
retain the organic layer in reacator
OL 826.4
388.90 DM water Lot-2 Wash the organic layer with DM 826 1215 0.5
water lot-2
Stir the reaction mass for 15-30 1215 1215 0.5

minutes.
Settle the reaction mass for 20-30 1215 1215 0.5

minutes
Aq Layer
388.90 DM water Lot-3 Wash the organic layer with sodium 826 1252 0.5
121.53 Sodium chloride chloride solution

minutes.

minutes
Aq Layer
Organic layer 826.41 Distillate
Distill off the solvent under vacuum 743.76695 83 826 10.0

of NLT 600 mmHg at below 55°C up
to 2 volume of input.
972.24 Hexane Lot-1 Charge Hexane Lot-1 into the reactor 83 1055 2.0
under stirring.
Maintain the reaction mass at 30 ± 1055 1055 2.0

5°C for 1-2 hours.
ML
Centrifuge
243.06 Hexane Lot-2 2.0

Wash the material with Hexane Lot-2
ML
Spin dry the wet materila till no ML 243.06 1.0
comes out of the centrifuse
F-PE-004/00-03.07.2009 Page 5 of 15
SERVICES
ISMS Class:Internal
ISMS Version:1.0
Unload the wet material into clean 1.0

poly bags and note the weight.
Load the wet material into the dryer 17.0

and Dry the wet material at 55 ± 5°C
for 12-15 hrs
Submit the sample to check water 4.0

content (Limit: NMT 1%) and LOD
(Limit: NMT 1%) as sample no
CMBG2-02 .
Note: If doesn’t complies continue the
drying at 55 ± 5°C and submit the
sample for every 4 h till it complies

complete analysis
CMBG-2
50.42 Totral Time Required for this stage, Hrs 76.3
No. of Days 3.18

Time
Tag Capacity Agitator Max
Sr.No Equipment Detail MOC Min vol Cycle Remarks
No. L/Size/Kg Type / RPM vol
hr
Reaction, Work
1 SSR … 2 Kl SS 316 PBT 83 1252 51.3
up and distillation
2 Nutch Filter … 200 Lt SS 317 … … … … Salt filtration
3 Centrifuse … 36" SS 316 … … … 8.0 Product Filtration

4 TD … 48 Trays SS 317 … … … 21.0 Product drying
F-PE-004/00-03.07.2009 Page 6 of 15
SERVICES
ISMS Class:Internal
ISMS Version:1.0
CMBG-2 CMBG-3

Mol. Wt 550.00 Mol. Wt 552.00
Yield W/W 0.86

Mole
Ratio
1 CMBG2 100 … 50.42 … 550.00 0.092 1 … 1.00 …

Dimethyl formamide Lot-
2 … 200 … 100.85 156.600 … … … 2.00 1.154
1Dimethyl formamide Lot-
3 … 800.00 … 403.39 40 … … … 8.00 …
2
4 Trifluoro acetic acid 310.88 203 156.76 102.45 … 1.375 15 3.11 2.03 1.53
5 Trifluoro acetic anhydride 30.4 20.27 15.33 10.22 … 0.073 0.8 0.30 0.20 1.50
6 Sodium cyanoborohydride 62.8 … 31.67 … 322 0.504 5.5 0.63 … …
7 Sodium bicarbonate Lot-1 480 … 242.03 … … … … 4.80 … …
8 DM water Lot-1 … 4000 … 2016.93 … … … … 40.00 …
9 Sodium bicarbonate Lot-2 180 … 90.76 … … … … 1.80 … …
10 DM water Lot-2 … 1500 … 756.35 … … … … 15.00 …
11 Toluene Lot-1 … 1000 … 504.23 … … … … 10.00 …
12 Toluene Lot-2 … 1000 … 504.23 … … … … 10.00 …
13 DM water Lot-3 … 1500 … 756.35 … … … … 15.00 …
14 Heptane Lot-1 … 800 … 403.39 … … … … 8.00 …
15 Heptane Lot-2 … 200 … 100.85 … … … … 2.00 …
Time
Min. Max.
Vol. Vol. Cycle
Send DMF lot-1 sample to QC for Hr.
WC as sample noCDBG3-01A
(NMT-0.5%)
Dimethyl formamide Lot-

100.8 Charge DMF Lot-1 into the reactor at 101 101 0.5
1
27.5 ± 2.5°C under N2 atmosphere
Cool the reaction mass to 2.5 ± 2.5°C 1.00
102.5 Trifluoro acetic acid Slowly add Trifluoro acetic acid drop 101 203 4.00
wise into the reactor at -5 ± 5°C under
Nitrogen atmosphere.
Note :Addition of Trifluoro acetic
acid is exothermic.

minutes at -5 ± 5°C.
10.2 Trifluoro acetic anhydride Slowly add Trifluoro acetic anhydride 203 214 2.0
drop wise into the reactor at -5 ± 5°C
under Nitrogen atmosphere.
Note :Addition of Trifluoro acetic
anhydride is exothermic.
Stir the mass for 5-10 minutes at -5 ± 214 214 0.25

5°C.
Send DMF lot-2 sample to QC for

WC as sample noCDBG3-01B
(NMT-0.5%)
403.39 Dimethyl formamide Lot-2 Charge Dimethyl formamide Lot-2

into the reactor under Nitrogen
atmosphere at 30 ± 5°C. 403 403 0.5
50.4 CMBG2 Charge CMBG2 into the reactor 403 419 0.5
under Nitrogen atmosphere at 30 ±
5°C.
Stir the reaction mass at 30 ± 5°C for

419 419 0.5
10-15 minutes.
Charge Sodium cyanoborohydride
31.7 Sodium cyanoborohydride under Nitrogen atmosphere at 30 ± 419 419 1.0
5°C.
Note:1.Charging of Sodium
cynoborohydride is exothermic.
419 419 0.25
Stir for 15-20 minutes at 30 ± 5°C.
419 419 1.0

Cool the reaction mass to -5 ± 5°C.
Slowly add above prepared solution

into the reactor at -5 ± 5°C . 419 632 3.0
Note :1. During addition white
F-PE-004/00-03.07.2009 precipitate formation is observed. Page 7 of 15
SERVICES
ISMS Class:Internal
Slowly add above prepared solution ISMS Version:1.0
into the reactor at -5 ± 5°C .
Note :1. During addition white
precipitate formation is observed.
Raise the reaction mass temperature

to 27.5 ± 2.5°C slowly in 3-4 hours.
Note:1.Reaction mass temperature
632 632 4.0
should brought to 27.5 ± 2.5 slowly in
3-4 hours to minimize the diol and
other isomer formation.
2.Reaction mass clear at 22°C-24°C.
Maintain the reaction mass at 27.5 ±

632 632 12.0
2.5°C for 10-12 hours.
Send sample to QC for TLC as CMBG-2 Content 632 632 1.0

CMBG3-01. NMT-3.0%
If complies
If TLC does not comply, maintain the 632 632 2.0
reaction mass at 27.5 ± 2.5°C till
TLC complies.Note : 1.Send sample
to QC for TLC as CMBG3-01 for
every 2 hours maintenance.
Cool the reaction mass to 22.5 ± 632 632 0.5

2.5°C.
F-PE-004/00-03.07.2009 Page 8 of 15
SERVICES
ISMS Class:Internal
ISMS Version:1.0
Charge Toluene Lot-1 into the reactor

504.2 Toluene Lot-1 632 1136 0.5
at 22.5 ± 2.5°C
2016.9 DM water Lot-1 Quench the reaction mass with

Na2CO3 solution at 22.5 ±
242.03 Sodium bicarbonate Lot-1 1136 3226 4.0
2.5°C.Note :1. Addition of Sodium
bicarbonate solution will be
exothermic in nature and CO2
effervescence/ frothing will be
observed.
Send sample to QC for pH as 0.5

CMBG3-02.pH : 8.0-9.0
If pH is below 8.0, Charge Sodium

bicarbonate solution into the reactor
at 22.5 ± 2.5°C. 3226 3226 0.5
Raise the mass temperature to 30 ±

5°C.
Stir the mass for 15-30 minutes. 3226 3226 0.5

minutes. 3226 3226 0.5

minutes
Org Layer
top organic layer in clean containers
AL 2706.4
504.2 Toluene Lot-2 Charge aqueous layer back into the 2706 3211 0.5
reactor.

minutes.

minutes
Org Layer
top organic layer in separate clean
containers
504.23 DM water Lot-2 Wash the organic layer with sodium 1024 1555 0.5
90.76 Sodium bicarbonate Lot-2 bicarbonate solution

minutes.

minutes
Aq Layer
Distill off the solvent at below 50° C 921.23097 102 1024 10.0
under vacuum up to 2.0 volumes of
the input remains in reactor.
403.39 Heptane Lot-1 Slowly charge the Heptane Lot-1 into 102 506 2.0
the reactor at 45 ± 5°C.
Note:.During the addition solid
formation is observed.
Stir the mass for 10-15 minutes at 45 506 506 1.0

± 5°C.
Cool to 27.5 ± 2.5°C with in 1-2

hours.
Stir the mass for 2-3 hours at 27.5 ±

2.5°C.
ML
Centrifuge/Nutch filter.
100.85 Heptane Lot-2 1.0

Wash the material with Hexane Lot-2
ML
F-PE-004/00-03.07.2009 Page 9 of 15
SERVICES
ISMS Class:Internal
ISMS Version:1.0
Spin dry the wet materila till no ML 100.85 1.0

comes out of the centrifuse
F-PE-004/00-03.07.2009 Page 10 of 15
SERVICES
ISMS Class:Internal
ISMS Version:1.0

Send sample to QC for water content 0.5

If not complies as CMBG3-03.NMT- 0.5%
Load the wet material into the dryer 8.0

and Dry the material at 42.5 ± 2.5°C
under vacuum of NLT 600 mmHg for
4-5 hours.
Submit the sample to check water 4.0

content (Limit: NMT 0.5%) as
sample no CMBG3-03 .
Note: If doesn’t complies continue the
drying at 42.5 ± 2.5°C and submit the
sample for every 4 h till it complies

complete analysis
CMBG-2
No. of Days 3.33

Time
hr
Reaction, Work
1 GLR … 3 KL SS 316 PBT 101 3226 64.5
up and distillation
Solution
2 GLR … 500 Lt SS 317 … … … …
Preparation
3 Centrifuse … 36" SS 316 … … … 6.0 Product Filtration
4 TD … 48 Trays SS 317 … … … 12.0 Product drying
F-PE-004/00-03.07.2009 Page 11 of 15
SERVICES
ISMS Class:Internal
ISMS Version:1.0
CMBG-3 CMBG-4

Mol. Wt 552.00 Mol. Wt 552.00
Yield W/W 0.77

Mole
Ratio
1 CMBG3 100 … 40.99 … 552.00 0.074 1 … 1.00 …

2 Dimethyl formamide 200 … 81.98 156.600 … … … 2.00 …
3 Imidazole Lot-1 … … X 68 … 7.2 … … …
4 Imidazole Lot-2 … … X* 68 … … … …
5 TBDPSC1 Lot-1 … … Y 275 0.238 3.2 … … …
6 TBDPSC1 Lot-2 … … Y* 275 … … … …
7 Toluene Lot-1 1000 0.00 409.91 … … … … … …
8 Toluene Lot-2 1000 … 409.91 … … … … 10.00 …
9 DM water Lot-1 1000 0.00 409.91 … … … … … …
10 DM water Lot-2 500 … 204.96 … … … … 5.00 …
11 DM water Lot-3 500 … 204.96 … … … … 5.00 …
12 Heptane Lot-1 800 … 327.93 … … … … 8.00 …
13 Heptane Lot-2 300 … 122.97 … … … … 3.00 …
14 Heptane Lot-3* 800 … 327.93 … … … … 8.00 …
15 Heptane Lot-4* 300 … 122.97 … … … … 3.00 …
Note :1.X and Y based on the OI and Diol in CMBG3.
2.X* and Y* based on the unreacted Diol and OI in CMBG4.
3.The above raw materials will be charged based on CMBG2 quantity.
Time
Min. Max.
Vol. Vol.
Cycle
Hr
Send sample to QC for water content of Raw
material (DMF-NMT:0.5%, CMBG3-NMT-0.5%,
Imidazole-NMT:0.5%) as sample No.CMBG4-
01A.
82.0 Dimethyl formamide 82 82 0.5

Charge Dimethyl formamide Lot-1 followed by
41.0 CMBG3 CMBG-3 into the reactor under N2 atmosphere at
30 ± 5°C.
X Imidazole Lot-1 82 82 0.25

Charge Imidazole Lot-1 into the reactor at 30 ± 5°C
under Nitrogen atmosphere. Note:1.Imidazole
Water content should be in NMT 0.5%.
2.Imidazole=(InputXsum of Diol &OI content) X 7.2 X 68.1
552
Stir the reaction mass for 10-15 minutes at 30 ± 82 82 0.25

5°C.
0.5
Cool the reaction mass to 22.5 ± 2.5°C.
Y TBDPSC1 Lot-1 82 82 1.0
Charge TBDPSCl Lot-1 into the reactor under

Nitrogen atmosphere at 22.5 ± 2.5°C.Charge
TBDPSCl Lot-1 into the reactor under Nitrogen
atmosphere at 22.5 ± 2.5°C.Note:1.
TBDPSCl=(InputXsum of Diol &OI content) X3.2X275
552
Slowly raise the reaction mass temperature to 52.5 82 82 1.00

± 2.5°C.
Maintain the reaction mass at 52.5 ± 2.5°C for 5-6

hours.
Send sample to QC for HPLC as Other isomer Content 82 82 1.5

CMBG4-01. NMT-1.0%
Diol Impurity
NMT:1.0 %
If complies
If HPLC does not comply 82 82 3.0
Cool the reaction mass to 30 ± 5°C. 82 82 1.0

F-PE-004/00-03.07.2009 Page 12 of 15
SERVICES
If complies
ISMS Class:Internal
ISMS Version:1.0
Cool the reaction mass to 30 ± 5°C.
F-PE-004/00-03.07.2009 Page 13 of 15
SERVICES
ISMS Class:Internal
ISMS Version:1.0
409.9 Toluene Lot-1 Charge Toluene Lot-1 and DM water 82 902 1.0
409.9 DM water Lot-1 lot-1 into the reactor at 30 ± 5°C.

minutes. 902 902 0.5

minutes
Org Layer
top organic layer in clean containers
AL 491.9
409.9 Toluene Lot-2 Charge aqueous layer back into the 492 902 0.5
reactor.

minutes.

minutes
Org Layer
retain the top organic layer inreactor
itself
Distill off the solvent at below 50° C 737.842887 82 820 14.0

under vacuum up to 2.0 volumes of
327.93 Heptane Lot-1 Distill off the solvent at below 50° C 82 410 2.0
under vacuum up to ~2.0 volumes of
Stir the mass for 5-10 minutes at 45 ± 410 410 1.0

5°C.
Cool the reaction mass to 27.5 ±

2.5°C.
Stir the mass for 1-2 hours at 27.5 ±

2.5°C.
ML
122.97 Heptane Lot-2 1.0

Wash the material with Heptane Lot-2
ML
Spin/suck dry the wet materila till no 122.97 1.0
F-PE-004/00-03.07.2009 Page 14 of 15
SERVICES
ISMS Class:Internal
ISMS Version:1.0

Send wet sample to QC for HPLC as CMBG-4 Purity:NLT-96.0% 2.0

If not complies CMBG4-02A. CMBG-2 Content NMT-2.0%
Other Isomer NMT-1.0%
Diol Impurity NMT-1.0%
327.93 Heptane Lot-3* Charge Heptane Lot-3 and wet cake
into the reactor. 1.0
Stir the mass for 1-2 hours at 27.5 ± 2.0

2.5°C.
ML
122.97 Heptane Lot-4* 1.0

Wash the material with Heptane Lot-4
ML
Spin/suck dry the wet materila till no 122.97 1.0

Send wet sample to QC for HPLC as CMBG-4 Purity:NLT-96.0% 2.0

CMBG4-02A. CMBG-2 Content NMT-2.0%
If complies Other Isomer NMT-1.0%
Diol Impurity NMT-1.0%
If not complies
If complies with limit load the

2.0
material into vacuum tray drier
Raise the temperature to 47.5 ± 2.5°C. 1.0
Dry the wet material at 47.5 ± 2.5°C 10.0

under vacuum of NLT 600 mmHg for
8-10 hours
Send sample to QC for Water content 1.0

(NMT-1.0%) and LOD(NMT-1.0%)
as CMBG4-02
If Water content and LOD does not

comply, dry the material at 42.5 ±
2.5°C under vacuum of 600 mmHg 5.0
till water content and LOD
complies.Send sample to QC for
Water content and LOD after every 4
hours drying as CMBG4-02.
Cool to 30 ± 5°C.Unload the wet 2.0

material into the cleaned HDPE
containers and note down the weight
and send sample to QC for COA
CMBG-2
No. of Days 2.25

Time
hr
Reaction, Work
1 … SS 316 PBT 82 902 47.0
up and distillation
Glass lined reactor 1 KL
2 Centrifuge … 48" SS 317 … … … 20.0 Product filtration
3 Vacuum Tray drier … 48 Trays SS 316 … … … 21.0 Product Drying
F-PE-004/00-03.07.2009 Page 15 of 15

MBG-1,2,3,4 All PFD

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CUSTOM PHARMACEUTICAL

Batch size 40.00 Kg Out put Weight in Kg 48.61 Kg

Lab Batch Plant Batch

1 CMPG4 100 40.00 … 311.00 0.129 1 … 1 …

120.0 Dimethyl formamide 160 160 1.0

Charge Camphorsulphonic acid

Raise the reaction mass 200 200 1.0

After addition, distill the by

Maintain the reaction mass at 65 ± 232 232 5.0

Send sample to QC for TLC as CMPG-4 Content 232 232 1.0

If TLC does not comply, maintain 232 232 1.0

Cool the reaction mass to 22.5 ± 232 232 1.0

16.0 Triethylamine Charge Triethyl amine into the

240.0 DM water Lot-1 232 632 1.0

Stir the reaction mass for 15 632 632 0.3

120.0 n-Hexane Lot-2 Slurry wash the material with n-

80.0 n-Hexane Lot-4 Spry Wash the material with n- 1.0

Unload the wet cake into the clean

Load the wet material into the 2.0

Dry the wet material under vacuum

Unload the semi dried material into 1.0

Load the semi dried material into 2.0

Raise the temperature to 67.5 ± 1.0

Dry the material at 67.5 ± 2.5°C for 15.0

Send sample to QC (NMT-1.0%)

If LOD and Water content does not 4.0

If complies with limit unload the

Totral Time Required for this stage, Hrs 58.3

No. of Days 2.43

Total Org.Effluent 320.00 Lt

Batch size 48.61 Kg Out put Weight in Kg 50.42 Kg

Lab Batch Plant Batch

1 CMBG1 100 48.61 … 429.50 0.113 1 … 1.00 …

Cool the reaction mass to 2.5 ± 2.5°C 1.00

Charge NMP into the reactor at 2.5 ±

Stir the reaction mass at 2.5 ± 2.5°C 0.5

Charge Tetra butyl ammonium

Slowly add 4-Methoxybezyl chloride 606 636 2.0

Stir the reaction mass at 2.5 ± 2.5°C

Raise the reaction mass tempreature 1.0

Maintain the reaction mass at 30 ± 8.0

Send sample to QC for TLC as CMBG-1 Content 636 636 1.0

If TLC does not comply, maintain the 636 636 2.0

Wash the oragic layer with DM water

Stir the reaction mass for 15-30

Settle the reaction mass for 30 1215 1215 0.5

Stir the reaction mass for 15-30 1215 1215 0.5

Settle the reaction mass for 20-30 1215 1215 0.5

Stir the reaction mass for 15-30 1252 1252 0.5

Settle the reaction mass for 20-30 1252 1252 0.5

Organic layer 826.41 Distillate

Distill off the solvent under vacuum 743.76695 83 826 10.0

Maintain the reaction mass at 30 ± 1055 1055 2.0

243.06 Hexane Lot-2 2.0

Unload the wet material into clean 1.0

Load the wet material into the dryer 17.0

Submit the sample to check water 4.0

If complies with limit unload the

No. of Days 3.18

Total Org.Effluent 1959.07 Lt

3 Centrifuse … 36" SS 316 … … … 8.0 Product Filtration

Batch size 50.42 Kg Out put Weight in Kg 40.99 Kg

Lab Batch Plant Batch