Reaction #368149

Reaction equation

sodium cyanoborohydride

tert-butyl 3(S)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate

acetic acid

ethyl 8-(1-benzyloxycarbonyl-4-piperidyl)-2-oxooctanoate

→

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

Yield 7.5%

Solvents

ethanol

ethanol

Conditions

Workup

1. 1
   workup.WAITAfter standing overnight at room temperature
2. 2
   Concentrationthe mixture is concentrated in vacuo
3. 3
   workup.ADDITIONdiluted with a mixture of water (100 ml) and ethyl acetate (200 ml)
4. 4
   workup.STIRRINGThe resulting mixture is agitated thoroughly
5. 5
   Filtrationfiltered
6. 6
   WashThe ethyl acetate layer is washed with water
7. 7
   Dryingdried over anhydrous magnesium sulfate
8. 8
   Concentrationconcentrated in vacuo
9. 9
   OtherThe oily residue is chromatographed on silica gel
10. 10
    OtherEvaporation of the first fraction

Procedure

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.

Source