Acetone → Clopidogrel Bisulfate

Participants

Reaction Steps

To a stirred suspension of clopidogrel base (3.83 g, 0.0119 mole) in water (3 mL) was added potassium hydrogen sulfate (1.62 g, 0.0119 mole) at 25-30° C. The reaction mixture was stirred for 15 minutes and acetone (25 mL) was added, further stirred for 30 minutes and filtered. The filtrate was distilled at 50-55° C. under reduce pressure (5-10 mm). Benzene (10 mL) was added to the reaction mixture and distilled at 90-95° C., di-isopropyl ether (20 mL) was added and stirred at 25-30° C. for 1 hour and filtered. The semi sold material was dissolved in dichloromethane (25 mL) and distilled under reduced pressure (5-10 mm) to give clopidogrel hydrogen sulfate (2.1 g). The amorphous form was similarly characterized by XRD, DSC, IR, chemical purity (HPLC)>99% and chiral purity (chiral HPLC) 99.5% (e.e.), % water 3.0, m.p. 94-98° C. (softens).

Provenance & Evidence