Sulfuric Acid → Clopidogrel bisulfate

Participants

Reaction Steps

Clopidogrel base (4.37 g, 1 eq.) was dissolved in dichloromethane (34.5 mL). Eighty percent aqueous sulfuric acid (1.06 mL, 1.1 eq.) was added to the solution at 20° C. The reaction mixture was heated to reflux temperature for 2 hours during which a turbid solution was formed. Then, the solution was cooled to room temperature and stirred at this temperature for an additional 16 hours during which a massive precipitate was formed. The white solid was collected by filtration, washed with dichloromethane (2×10 ml) and dried at 50° C. in a vacuum oven for 24 hours to obtain 2.76 g (48%) of clopidogrel hydrogensulfate crystal form II.

Provenance & Evidence