Sulfuric Acid → Clopidogrel Bisulfate

Participants

Reaction Steps

Clopidogrel base (5.01 g, 1 eq.) was dissolved in methylethyl ketone (MEK) (39.5 mL). Eighty percent aqueous sulfuric acid (0.74 mL, 0.66 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 half of the amount of the solvent was evaporated under reduced pressure 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 3.55 g (54%) of clopidogrel hydrogensulfate crystal form II.

Provenance & Evidence