Sulfuric Acid → Clopidogrel Bisulfate

Participants

Reaction Steps

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).

Provenance & Evidence