Sulfuric Acid → Clopidogrel bisulfate

HRID 253073Notes

Reaction equation

HRID 253073 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])(=[O:25])([OH:24])[OH:23]>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 2

HCID 1118Sulfuric AcidHCID 60606Clopidogrel

Product 1

HCID 115366Clopidogrel bisulfateYield 105.2%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

To a solution of Clopidogrel free base (10 g, 0.031 moles) in acetone (65 ml) and water (13 ml), was added dropwise sulfuric acid (3.0 g, 0.33 mole) at 25-30° C. The solution was stirred for 15 minutes, distilled at 50-55° C. under reduced pressure (5-10 mm). Dichloromethane (100 ml) was added and distilled, the operation was repeated twice using dichloromethane (100 ml). Finally traces of water was removed under reduced pressure (5-10 mm) to give amorphous clopidogrel hydrogen sulfate (13.7 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 1.95, m.p. 110-120° C. (softens).

Workup

  1. distillationdistilled at 50-55° C. under reduced pressure (5-10 mm)
  2. additionDichloromethane (100 ml) was added
  3. distillationdistilled
  4. customwas removed under reduced pressure (5-10 mm)

Sources & evidence

ORD record
ord-fc66b892ede044daa4325e9003ebc613
Source dataset
uspto-grants-2011_01
Patent number
US07872019B2

Reaction notes

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