Sulfuric Acid → Clopidogrel Bisulfate

Participants

Reaction Steps

Clopidogrel base (4.27 g, 1 eq.) was dissolved in methylethyl ketone (MEK) (33.7 ml). Eighty percent aqueous sulfuric acid (1.03 ml, 1.1 eq.) was added to the solution at 20° C. The reaction mixture was heated to reflux temperature for 2 hours. Then, the solution was cooled to room temperature and stirred at this temperature for additional 67 hours during which a precipitate was formed. The white solid was collected by filtration, washed with MEK (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