Iodine → (E)-3-cyclopentyl-2-iodo-acrylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of lithium chloride (8.48 g, 200 mmol, predried at 130° C. under high vacuum for 2 h) and copper cyanide (8.96 g, 100 mmol) in dry tetrahydrofuran (100 mL) was stirred at 25° C. under argon for 10 min to obtain a clear solution. The reaction mixture was cooled to −70° C. and then slowly treated with a 2M solution of cyclopentylmagnesium chloride in diethyl ether (55 mL, 110 mmol). After addition, the reaction mixture was allowed to warm to −30° C. where it was stirred for 5 min. The resulting reaction mixture was again cooled back to −70° C. and then slowly treated with methyl propiolate (7.99 g, 95 mmol). The reaction mixture was stirred for at −60° C. to −50° C. overnight and then cooled to −70° C. to −60° C., at which time, the reaction mixture was treated slowly with a solution of iodine (34.3 g, 135 mmol) in dry tetrahydrofuran (30 mL). After addition of the iodine solution, the cooling bath was removed, and the reaction mixture was allowed to warm to 25° C. where it was stirred for 2 h. The reaction mixture was then poured into a solution consisting of a saturated aqueous ammonium chloride solution (200 mL) and ammonium hydroxide (50 mL), and the organic compound was extracted into diethyl ether (3×100 mL). The combined organic extracts were successively washed with a saturated aqueous sodium thiosulfate solution (1×300 mL) and a saturated aqueous sodium chloride solution (1×300 mL). The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 20/1 hexanes/diethyl ether) afforded (E)-3-cyclopentyl-2-iodo-acrylic acid methyl ester (25.8 g, 97%) as an yellow oil: EI-HRMS m/e calcd for C9H13IO2 (M+) 279.9960, found 279.9961.

Provenance & Evidence