Sulfuric Acid → Clopidogrel Bisulfate

Participants

Reaction Steps

Clopidogrel base (2.89 g) was dissolved in isopropanol (44 mL). Eighty percent aqueous sulfuric acid (0.42 mL) was added to the solution at 20° C. The reaction mixture was heated to reflux temperature for 2 hours. The solution was cooled to room temperature and stirred at this temperature for an additional 5 hours. Then half of the solvent was removed by evaporation under reduced pressure and the resulting solution was stirred at room temperature for 45 minutes to obtain a white precipitate. The solid was collected by filtration, washed with IPA (3×10 ml) and dried at 50° C. in a vacuum oven for 15 hours to obtain 1.24 g (33%) of clopidogrel hydrogensulfate crystal Form IV.

Provenance & Evidence