Acetic Acid → tert-butyl 3(S)-[7-(1-benzyloxycarbonyl-4-piperidyl)-1(R)-ethoxycarbonylheptyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate

A mixture of tert-butyl 3(S)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate (2 g), ethanol (10 ml), acetic acid (0.49 g), ethyl 8-(1-benzyloxycarbonyl-4-piperidyl)-2-oxooctanoate (3 g) and molecular sieves 3A (10 g) is stirred for 10 minutes. To the stirred mixture is added dropwise a solution of sodium cyanoborohydride (0.47 g) in ethanol (40 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 (100 ml) and ethyl acetate (200 ml). The resulting mixture is agitated thoroughly and filtered. The ethyl acetate layer is washed with water, dried over anhydrous magnesium sulfate and concentrated in vacuo. The oily residue is chromatographed on silica gel using hexane-ethyl acetate (5:2-2:1) as an eluent. Evaporation of the first fraction affords tert-butyl 3(S)-[7-(1-benzyloxycarbonyl-4-piperidyl)-1(R)-ethoxycarbonylheptyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate (0.35 g) as a colorless oil.

1. waitAfter standing overnight at room temperature
2. concentrationthe mixture is concentrated in vacuo
3. additiondiluted with a mixture of water (100 ml) and ethyl acetate (200 ml)
4. stirringThe resulting mixture is agitated thoroughly
5. filtrationfiltered
6. washThe ethyl acetate layer is washed with water
7. dry with materialdried over anhydrous magnesium sulfate
8. concentrationconcentrated in vacuo
9. customThe oily residue is chromatographed on silica gel
10. customEvaporation of the first fraction

ORDレコード

ord-09fc1eaa38194dedb02d6769ac546b4d

出典データセット

uspto-grants-1985_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US04548932