benzyl 3(S)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1(R)-ethoxycarbonylpentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate → 3(S)-[1(R)-carboxy-5-(4-piperidyl)pentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetic acid

참여 물질

반응 단계

A solution of benzyl 3(S)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1(R)-ethoxycarbonylpentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate (0.35 g) in ethanol (20 ml) is subjected to catalytic hydrogenolysis over 10% palladium carbon (0.5 g, 50% wet) at ambient temperature and pressure until the absorption of hydrogen ceases. After removal of the catalyst by filtration, the filtrate is concentrated. To the residue is added 5N hydrogen chloride-ethyl acetate solution (1 ml), and the resulting mixture is diluted with ethyl ether (50 ml) to deposit 3(S)-[1(R)-ethoxycarbonyl-5-(4-piperidyl)pentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetic acid dihydrochloride (0.25 g) as the colorless precipitate. This acid is dissolved in 1N sodium hydroxide solution (10 ml), and the resulting solution is allowed to stand for 30 minutes at room temperature. After addition of acetic acid (2 ml), the mixture is subjected to MCI gel column chromatography using water-methanol (2:1) as an eluent. The eluate is concentrated in vacuo and lyophilized to yield 3(S)-[1(R)-carboxy-5-(4-piperidyl)pentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetic acid (0.5 g) as colorless powder.

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