Sulfuric Acid → Atazanavir Sulfate

Participants

Reaction Conditions

Reaction Steps

14.2 mL of sulfuric acid (5 M, 1.0 equiv) was added into the solution of 50 g of atazanavir base and 350 mL of IPA (7 vol) at 40-50° C. After the resulting amber solution was clear, it was filtered and washed with 50 mL of IPA (1 vol). 40 mL of IPAc (4 vol.) and atazanavir sulfate in Form A (0.7% wt) was added into the resulting clear amber solution at 40-50° C. and then stirred at 40-50° C. for 1 hr. The resulting slurry was cooled to 20-30° C. 80 mL of IPAc (8 vol) was added into the solution and then stirred at 20-30° C. for 4 hr. The product was filtered, washed with a mixture of IPA/IPAc (1:1, 100 mL, 2 vol), and dried under vacuum at 40-50° C. for 16 hr to afford atazanavir sulfate in Form A (86% yield, >99.9% HPLC purity).

Provenance & Evidence