Hydrochloric Acid → N-(5-chloro-thiazol-2-yl)-3-cyclopentyl-2(R)-(4-methanesulfonyl-phenyl)-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of triphenylphosphine (4.60 g, 17.55 mmol) in methylene chloride (50 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (3.12 g, 17.55 mmol). The reaction mixture was stirred at 0° C. for 25 min and then treated with 3-cyclopentyl-2(R)-(4-methanesulfonylphenyl)propionic acid (prepared as in Example 128, 4.00 g, 13.50 mmol). The resulting reaction mixture was stirred at 0° C. for 15 min and then allowed to warm to 25° C. where it was stirred for 30 min. The reaction mixture was then treated with a solution of 2-amino-5-chlorothiazole hydrochloride (5.77 g, 33.75 mmol) and pyridine (4.37 mL, 54.03 mmol) in methylene chloride. The resulting reaction mixture was allowed to stir at 25° C. overnight. The reaction mixture was then diluted with water (150 mL), a 1N aqueous hydrochloric acid solution (50 mL), and ethyl acetate (100 mL). The layers were separated. The organic layer was washed with a saturated aqueous sodium bicarbonate solution (2×50 mL) and then dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/1 hexanes/ethyl acetate) afforded N-(5-chloro-thiazol-2-yl)-3-cyclopentyl-2(R)-(4-methanesulfonyl-phenyl)-propionamide (2.24 g, 40%) as a yellow foam: mp 83-88° C. (foam to gel); [α]23589=−73.3° (c=1, chloroform); EI-HRMS m/e calcd for C18H21ClN2O3S2 (M+) 412.0682, found 412.0692.

Provenance & Evidence