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 1 hour. (αS,7RS)-methyl-α-(7-hydroxy-4,5,6,7-tetrahydro-5-thieno[3,2-c]pyridyl)-o-chlorophenylacetate para toluenesulfonic acid salt (55.0 g, 108 mmol) is added to the mixture at 0–5° C. After the addition is complete the mixture is warmed to room temperature and stirred for 17 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 oily product (30.6 g). The product obtained was found to be identical to the product obtained in Example 1 by 1H-NMR.

Provenance & Evidence