Sulfuric Acid → Clopidogrel Bisulfate

Participants

Reaction Steps

Clopidogrel base (4.17 g, 1 eq.) was dissolved in 1,4-Dioxane (32.9 mL). Eighty percent aqueous sulfuric acid (0.61 ml, 0.66 eq.) was added to the solution at 20° C. The reaction mixture was heated to reflux temperature for 2 hours during which a massive precipitate was formed. Then, the solution was cooled to room temperature and stirred at this temperature for additional 2 hours. The white solid was collected by filtration, washed with 1,4-dioxane (2×10 mL) and dried at 50° C. in a vacuum oven for 24 hours to obtain 2.61 g (48%) of clopidogrel hydrogensulfate crystal form II.

Provenance & Evidence