Sodium Iodide → Clopidogrel

Participants

Reaction Steps

To a mixture of sodium iodide in dichloromethane is added chlorotriethylsilane. The mixture is stirred at room temperature under nitrogen for 90 min. A solution of (αS,7RS)-methyl-α-(7-hydroxy-4,5,6,7-tetrahydro-5-thieno[3,2-c]pyridyl)-o-chlorophenylacetate (9) (8.2 g, 24.3 mmol) in dichloromethane is added to the mixture at 0–5° C. After the addition is complete the mixture is warmed to room temperature and stirred for 3 hours. Water is then added to the mixture at 0–5° C. 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 oily product (6.69 g). The product obtained was found to be identical to the product obtained in Example 1 by 1H-NMR.

Provenance & Evidence