Sulfuric Acid → Clopidogrel hydrogen sulfate

Participants

Reaction Conditions

Reaction Steps

5 g of (+)-(2-chlorophenyl)-(6,7-dihydro-4H-thieno[3,2-c]pyrid-5-yl)acetamide was dissolved in 20 ml methanol and the solution warmed to 65 to 70° C. 15 mL (0.28 mol) of chilled conc. H2SO4 (98%, −15° C.) was added slowly in 1 hr maintaining the temperature till −15° C. After the completion of addition the reaction mixture was heated at 70° C. for 16 hrs. The solvent was distilled off under reduced pressure and to the residue 50 mL of water was added and stirred for 30 min followed by cooling to −5° C. The pH of reaction mixture was adjusted between 9 to 10 using aq. sodium carbonate. The residue was extracted with 100 mL ethyl acetate. The organic layer was dried over anhydrous Na2SO4, and evaporated under vacuum. The combined eluent was evaporated at reduced pressure to yield 2.8 g of crude product purified by column chromatography, using hexane:ethyl acetate (9:1) as eluent to give 2 g of titled compound (1) and 1 g of the starting material (S)-(+)-(II).

Provenance & Evidence