Oxalyl chloride → (2R,3R)-N,N-bis-(tert-butoxycarbonylmethyl)-2,3-epoxybutyramide

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Reaction Steps

A solution of 11.6 g of oxalyl chloride in 25 ml of methylene chloride is added dropwise, in the course of 15 minutes, to a mixture, cooled to -25°, of 20 g of dimethylforinaniide and 115 ml of methylene chloride. The white suspension is stirred for a further 20 minutes at -25°, and a solution of 28.5 g of the dicyclohexylammonium salt of (2R,3R,)-2,3-epoxybutyric acid in 115 ml of methylene chloride is then added in the course of 10 minutes. The reaction mixture is stirred for a further 20 minutes at the same temperature, and a solution of 17.87 g of di-tert-butyl iminodiacetate in 90 ml of methylene chloride and 9.22 ml of N-methylmorpholine are then added dropwise simultaneously in the course of 15 minutes. The cooling bath is removed and the reaction mixture is stirred for 3 hours at room temperature. The white suspension is then filtered through a sintered glass suction filer, the residue is washed with methylene chloride, and the filtrate is diluted with methylene chloride and washed successively with water, 5% aqueous citric acid, saturated aqueous sodium bicarbonate solution and water. The aqueous phases are subsequently extracted twice with methylene chloride, and the combined organic phases are dried and evaporated under a water pump vacuum. The yellow-brown crude product is purified by flash chromatography over silica gel (Merck 9385) using a 9:1 mixture of methylene chloride and ethyl acetate as the mobile phase. (2R,3R)-N,N-Bis-(tert-butoxy-carbonylmethyl)-2,3-epoxybutyramide is obtained in the form of a pale yellow oil, [α]D =+52° (c=1.250% in chloroform).

Provenance & Evidence