Acetone → Clopidogrel Bisulfate

Participants

Reaction Steps

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).

Provenance & Evidence