Hexane → (3S,4S,1R)-4-tert-butoxycarbonyl-1-tert-butoxycarbonylmethyl-3-(1'-hydroxyethyl)-azetidin-2-one

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Reaction Steps

A solution of 13.18 g of (2R,3R)-N,N-bis-(tert-butoxycarbonylmethyl)-2,3-epoxybutyramide in 100 ml of tetrahydrofuran is cooled with stirring to -15°, and 100 ml of a 0.5-molar solution of lithium hexamethyldisilazide in tetrahydrofiran is added at temperatures between -15° and -10°. The progress of the reaction is followed by thin layer chromatography (solvent: a 1:1 mixture of hexane and ethyl acetate); the reaction is complete after stirring for about 4 hours at the temperature indicated above. The reaction mixture is diluted with methylene chloride and poured onto ice, and the organic layer is washed successively with water, twice with 0.1N hydrochloric acid, water, saturated aqueous sodium bicarbonate solution and water. The wash water is extracted twice with methylene chloride, and the combined organic phases are dried over sodium sulfate and evaporated under a water pump vacuum. After flash chromatography over 750 g of silica gel 60 (0.040-0.063 mm, Merck; elution with a 6:4 mixture of hexane and ethyl acetate), the crude product obtained gives (3S,4S,1R)-4-tert-butoxycarbonyl-1-tert-butoxycarbonylmethyl-3-(1'-hydroxyethyl)-azetidin-2-one, which melts at 79°-81°; [α]D -22.6° (c=0.574% in chloroform).

Provenance & Evidence