Sulfuric Acid → Clopidogrel Bisulfate

Participants

Reaction Steps

Clopidogrel base (5.31 g, leq.) was dissolved in ethyl acetate (41.9 mL). Eighty percent aqueous sulfuric acid (1.29 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 massive precipitate was formed. Then, the solution was cooled to room temperature and stirred at this temperature for an additional 3 hours. The white solid was collected by filtration, washed with ethyl acetate (2×10 ml) and dried at 50° C. in a vacuum oven for 24 hours to obtain 4.60 g (66%) of clopidogrel hydrogensulfate crystal Form II.

Provenance & Evidence