Pyridine → N-[[[4-[2-chloro-4-(trifluoromethyl)phenoxy]-2-fluorophenyl]amino]thio]-L-proline, methyl ester

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Reaction Steps

A solution of 11.3 g of sulphur dichloride in 20 ml of dichloromethane was added at room temperature over 15 minutes to a stirred solution of 16.6 g of L-proline, methyl ester hydrochloride in 50 ml of the same solvent, following which a solution of 17.4 g of pyridine in 20 ml of the same solvent was added to the reaction mixture over 30 minutes. After stirring overnight, the mixture was diluted with 150 ml of diethyl ether, filtered, and stripped of solvent to leave 17.8 g of the crude product. 4.3 g of this product was dissolved in 10 ml of diethyl ether and added over 15 minutes at room temperature to a stirred mixture of 6.1 g of 31, 2.2 g of triethylamine and 50 ml of diethyl ether. After stirring at room temperature for 30 minutes, 250 ml of diethyl ether was added, and the mixture was washed with water, dried and stripped of solvent. The residue was chromatographed over silica using a mixture of diethyl ether and petroleum ether as eluent, to give 34, as a brown oil.

Provenance & Evidence