Sulfuric Acid → Clopidogrel Bisulfate

Participants

Reaction Steps

Clopidogrel base (4.29 g, 1 eq.) was dissolved in toluene (33.8 mL). Eighty percent aqueous sulfuric acid (1.04 mL, 1.1 eq.) was added to the solution at 20° C. The reaction mixture was heated to reflux temperature for 3 hours. 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 toluene (2×10 ml) and dried at 50° C. in a vacuum oven for 24 hours to obtain 4.59 g (82%) of clopidogrel hydrogensulfate crystal form II.

Provenance & Evidence