Acetone → Clopidogrel bisulfate

HRID 253070Notes

Reaction equation

HRID 253070 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]([N:13]1[CH2:21][C:17]2[CH:18]=[CH:19][S:20][C:16]=2[CH2:15][CH2:14]1)[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][C:11]=1[Cl:12])=[O:4].[S:22]([O-:26])([OH:25])(=[O:24])=[O:23].[K+].CC(C)=O>O>[CH3:1][O:2][C:3]([C@@H:5]([N:13]1[CH2:21][C:17]2[CH:18]=[CH:19][S:20][C:16]=2[CH2:15][CH2:14]1)[C:6]1[C:11]([Cl:12])=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:4].[OH:25][S:22]([OH:26])(=[O:24])=[O:23]

Participants

5

Reactant 3

HCID 180AcetoneHCID 60606ClopidogrelHCID 516920Potassium bisulfate

Product 1

HCID 115366Clopidogrel bisulfateYield 92.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred suspension of clopidogrel base (38.31 g, 0.119 mole) in water (30 mL), was added potassium hydrogen sulfate (32.3 g, 0.237 mole) at 25-30° C. The reaction mixture was stirred for 15 minutes and acetone (250 mL) was added, stirred further for 30 minutes and filtered. Insoluble solid was filtered. The filtrate was distilled at 50-55° C. under reduced pressure (5-10 mm). Dichloromethane (380 mL) was added and distilled at 50-55° C. This operation was repeated twice by adding dichloromethane (350 mL), and finally traces of water was removed under reduce pressure (5-10 mm) to give amorphous clopidogrel hydrogen sulfate (46 g). The amorphous form was similarly characterized by XRD, DSC, IR, chemical purity (HPLC)>99% and chiral purity (chiral HPLC) 99.8% (e.e.), % water 1.91, m.p. 132-135° C. (softens).

Workup

  1. stirringstirred further for 30 minutes
  2. filtrationfiltered
  3. filtrationInsoluble solid was filtered
  4. distillationThe filtrate was distilled at 50-55° C. under reduced pressure (5-10 mm)
  5. additionDichloromethane (380 mL) was added
  6. distillationdistilled at 50-55° C
  7. additionby adding dichloromethane (350 mL)
  8. customwas removed

Sources & evidence

ORD record
ord-48d64f674b1e48f6941d7ea8ccc4f1b2
Source dataset
uspto-grants-2011_01
Patent number
US07872019B2

Reaction notes

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