Hydrochloric Acid → 3-Cyclopentyl-2-(4-methylsulfanyl-phenyl)-acrylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

A suspension of cyclopentylmethyl triphenylphosphonium iodide (151.73 g, 0.321 mol) in dry tetrahydrofuran (494 mL) was cooled to 0° C. and then treated slowly with a 1.0 M solution of lithium bis(trimethylsilyl)amide (309 mL, 0.309 mol). The bright orange reaction mixture was stirred at 0° C. for 1 h. The reaction mixture was then treated with a solution of (4-methylsulfanyl-phenyl)-oxo-acetic acid ethyl ester (55.42 g, 0.247 mol) in dry tetrahydrofuran (100 mL) in small portions. The resulting reaction mixture was stirred at 0° C. for 30 min and then allowed to warm to 25° C. where it was stirred for 6 h. The reaction mixture was then diluted with water (500 mL), at which time, the reaction mixture indicated a pH=11. The reaction mixture was adjusted to pH=6 with a 10% aqueous hydrochloric acid solution and then allowed to sit at 25° C. overnight. The reaction mixture was concentrated in vacuo to remove tetrahydrofuran and then diluted with diethyl ether (1 L). A solid began to precipitate, and the reaction mixture was allowed to sit at 25° C. for 1 h. The solid was filtered and washed well with diethyl ether. The resulting two-layer filtrate was transferred to a separatory funnel, and the layers were separated. The aqueous layer was further extracted with diethyl ether (1×500 mL). The combined organic layers were washed with a saturated aqueous sodium chloride solution (1×500 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Purification using a plug of silica (Merck Silica gel 60, 230-400 mesh, 9/1 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(4-methylsulfanyl-phenyl)-acrylic acid ethyl ester (58.93 g, 82%) as a yellow oil consisting of a 1.44:1 mixture of (E):(Z) isomers. The material was used without further separation and characterization.

Provenance & Evidence