Sulfuric Acid → Clopidogrel Bisulfate

Participants

Reaction Steps

Clopidogrel base (4.39 g, 1 eq.) was dissolved in tert-butylmethyl ether (MTBE) (34.6 ml). Eighty percent aqueous sulfuric acid (0.64 ml, 0.66 eq.) was added to the solution at 20° C. The reaction mixture was heated to reflux temperature for 3 hours during which a sticky precipitate was formed. Then, the solution was cooled to room temperature and stirred at this temperature for an additional 2 hours. The obtained white solid was collected by filtration, washed with MTBE (2×10 mL) and dried at 50° C. in a vacuum oven for 24 hours to obtain 2.96 g (52%) of clopidogrel hydrogensulfate crystal form II.

Provenance & Evidence