Sulfuric Acid → Clopidogrel Bisulfate

Participants

Reaction Steps

Clopidogrel base (2.86 g, 1 eq.) was dissolved in 1-Propanol (22.6 mL). Eighty percent aqueous sulfuric acid (0.59 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 stirred at this temperature for additional 16 hours. The solvent was evaporated to dryness under reduced pressure to obtain an oily residue. To the residue, MTBE (50 mL) was added and the resulting mixture was stirred at room temperature for 24 hours during which a massive precipitate was formed. The white solid was collected by filtration, washed with MTBE (2×10 mL) and dried at 50° C. in a vacuum oven for 30 hours to obtain 2.58 g (69%) of clopidogrel hydrogensulfate crystal Form VI.

Provenance & Evidence