Sodium Iodide → Clopidogrel

Participants

Reaction Steps

To a mixture of sodium iodide in acetonitrile is added chlorotrimethylsilane. The mixture is stirred at room temperature under nitrogen for 30 minutes. A solution of (αS,7RS)-methyl-α-(7-hydroxy-4,5,6,7-tetrahydro-5-thieno[3,2-c]pyridyl)-o-chlorophenylacetate (9) (23.4 g, 69.3 mmol) in toluene and acetonitrile is added to the mixture at 0–5° C. After the addition is complete the mixture is warmed to room temperature and stirred for 2 hours. Water is then added to the mixture at 0–5° C. The mixture is then warmed again to room temperature and stirred for an additional 4 hours. The reaction mixture is then basified with aqueous sodium bicarbonate solution. The organic layer is then washed with aqueous sodium thiosulfate solution, followed by water, then brine. The organic layer is then dried, filtered and concentrated to provide clopidogrel free base as an oil product (21.4 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) 3.5–4.0 (2H, m), 3.75 (3H, s), 2.9 (4H, s); chiral HPLC 99:1 enantiomeric ratio.

Provenance & Evidence