Ethyl chloroformate → Ethyl 3-(1-tert-butoxycarbonylaminocyclopropyl)propiolate

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, chloromethyltrimethylphosphonium chloride (5.156 g, 14.85 mmol) was suspended in anhydrous tetrahydrofuran (30 ml) to which, after cooling to −55° C., was subsequently added dropwise a 1.68 M n-butyl lithium n-hexane solution (8.87 ml, 14.90 mmol) over a period of 5 minutes. The reaction suspension was stirred for 30 minutes in an ice bath and for 3 hours at room temperature and then cooled to −55° C. To the reaction suspension was added dropwise an anhydrous tetrahydrofuran (10 ml) solution of 1-tert-butoxycarbonylaminocyclopropane carbaldehyde (2.498 g, 13.50 mmol) over a period of 10 minutes, subsequently stirring the mixture for 1 hour at −50° C. and then for 30 minutes in an ice bath. The reaction suspension was cooled to −78° C., an n-hexane solution of 1.68 M an n-butyl lithium (17.68 ml, 29.70 mmol) was added dropwise thereto over a period of 10 minutes and then the mixture was stirred at −78° C. for 20 minutes. Ethyl chloroformate (1.61 ml, 16.88 mmol) was added dropwise to the reaction suspension which was subsequently stirred for 1.5 hours at −78° C. and then for 1 hour in an ice bath. While cooling in an ice bath, the reaction suspension was mixed-with saturated brine (30 ml), the organic layer was separated and the aqueous layer was extracted with diethyl ether (30 ml×2). The organic layers were combined, washed with saturated brine (30 ml) and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the resulting residue was applied to a flash silica gel chromatography column and eluted with an eluant of n-hexane:ethyl acetate=5:1, to-thereby obtain 2.178 g (63.9%) of the title compound as a colorless oil.

Provenance & Evidence