Sulfuric Acid → Clopidogrel Bisulfate

Participants

Reaction Steps

Clopidogrel base (4.28 g) was dissolved in 1-butanol (16.9 ml). Eighty percent aqueous sulfuric acid (0.63 ml) 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 the solvent was evaporated to dryness under reduced pressure leaving yellow oil. The oil was stirred in methyl t-butyl ether (MTBE) (125 ml) for 96 hours at room temperature to obtain a precipitate. The 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 3.33 g (60%) of clopidogrel hydrogensulfate crystal Form III.

Provenance & Evidence