Hydrochloric Acid → Clopidogrel

Participants

Reaction Steps

Methyl(S)-α-(7-hydroxy-4,5,6,7-tetrahydro-5-thieno[3,2-c]pyridyl)-o-chlorophenylacetate (1 g, 2.95 mmol) was dissolved in acetic acid (18.8 mL) and treated sequentially with conc. HCl and SnCl2 dihydrate (1.4 g, 6.2 mmol). The reaction was allowed to stir under nitrogen and the solvent was evaporated under vacuum after its completion. The residue was basified with aqueous sodium bicarbonate and extracted repeatedly with ethyl acetate. The combined organic layer was dried, filtered and concentrated to provide clopidogrel free base as an oily product (0.75 g). 1H-NMR (CDCl3, ppm) 7.7 (1H, dd), 7.35 (1H, m), 7.2-7-35 (2H, m), 7.2 (1H, d), 6.68 (1H, dd), 4.95 (1H, s), 4.68 (1H, bs), 3.5-4.0 (2H, m), 3.75 (3H, s), 2.9 (4H, s); chiral HPLC 98:2 enantiomeric ratio.

Provenance & Evidence