Acetamidomalonic acid diethyl ester → Diethyl 5-isoxazolylmethylacetamidomalonate

Participants

Reaction Steps

3.1 g (70.7 mmole) of sodium hydride (as a 55% w/w dispersion in mineral oil) were added to a solution of 14.0 g (6,43 mmole) of diethyl acetamidomalonate dissolved in 150 ml of dimethylformamide, whilst ice-cooling, and the mixture was stirred for 1 hour. At the end of this time, 23.9 g (0.148 mmole) of 5-bromomethylisoxazole were added to the reaction mixture, which was then stirred at room temperature for 4.5 hours, The reaction mixture was then concentrated by evaporation under reduced pressure, and the residue was mixed with water and extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, after which it was concentrated by evaporation under reduced pressure. The residue was purified by silica gel column chromatography (eluent: a 1: 2 by volume mixture of ethyl acetate and hexane), to afford 14.78 g (77.1%) of the title compound, melting at 75°-76° C.

Provenance & Evidence