Sulfuric Acid → Clopidogrel Bisulfate

Participants

Reaction Steps

Clopidogrel base (3.85 g) was dissolved in absolute ethanol (30.4 mL). Eighty percent aqueous sulfuric acid (0.56 mL) was added to the solution. 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 a white foam. The foam was stirred in methyl t-butyl ether (MTBE) (70 ml) for 3 hours at room temperature. Approximately half of the MTBE was evaporated under reduced pressure and a solid was recovered by filtration. The solid was dried at 50° C. in a vacuum oven to obtain 2.82 g (56%) of a mixture of clopidogrel hydrogensulfate crystal form I and amorphous clopidogrel hydrogensulfate.

Provenance & Evidence