Acetic Acid → tert-butyl 3(S)-[6(1-benzyloxycarbonyl-4-piperidyl)-1(R)-ethoxycarbonylhexyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate

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Reaction Steps

A mixture of tert-butyl 3(S)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate (2.4 l g), ethanol (30 ml), acetic acid (0.5 g), ethyl 7-(1-benzyloxycarbonyl-4-piperidyl)-2-oxoheptanoate (3.2 g) and molecular sieves 3A (10 g) is stirred for 10 minutes. To the stirred mixture is added dropwise a solution of sodium cyanoborohydride (0.51 g) in ethanol (50 ml) for 3 hours at room temperature. After standing overnight at room temperature, the mixture is concentrated in vacuo and diluted with a mixture of water (50 ml) and ethyl acetate (200 ml). The resulting mixture is agitated thoroughly and filtered. The ethyl acetate layer is washed successively with 0.1N hydrochloric acid, 0.1N sodium hydroxide solution and water, dried over anhydrous magnesium sulfate and concentrated in vacuo. The oily residue is chromatographed on silica gel using hexane-ethyl acetate (2:1) as an eluent. Evaporation of the first fraction affords tert-butyl 3(S)-[6-(1-benzyloxycarbonyl-4-piperidyl)-1(R)-ethoxycarbonylhexyl]amino-4-oxo-2,3,4,5 -tetrahydro-1,5-benzoxazepine-5-acetate (0.35 g) as a colorless oil.

Provenance & Evidence