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

HRID 280967Notes

Reaction equation

HRID 280967 reaction equation
[NH2:1][C@@H:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:6]2[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=2[O:4][CH2:3]1.C(O)(=O)C.[CH2:26]([O:33][C:34]([N:36]1[CH2:41][CH2:40][CH:39]([CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][C:48](=O)[C:49]([O:51][CH2:52][CH3:53])=[O:50])[CH2:38][CH2:37]1)=[O:35])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C([BH3-])#N.[Na+]>C(O)C>[CH2:26]([O:33][C:34]([N:36]1[CH2:37][CH2:38][CH:39]([CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][C@@H:48]([NH:1][C@@H:2]2[C:8](=[O:9])[N:7]([CH2:10][C:11]([O:13][C:14]([CH3:16])([CH3:17])[CH3:15])=[O:12])[C:6]3[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=3[O:4][CH2:3]2)[C:49]([O:51][CH2:52][CH3:53])=[O:50])[CH2:40][CH2:41]1)=[O:35])[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 13622530tert-butyl 3(S)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetateHCID 20143649Ethyl 8-(1-benzyloxycarbonyl-4-piperidyl)-2-oxooctanoate

Product 1

HCID 54333033tert-butyl 3(S)-[7-(1-benzyloxycarbonyl-4-piperidyl)-1(R)-ethoxycarbonylheptyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetateYield 7.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

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.

Workup

  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

Sources & evidence

ORD record
ord-cb589e065895435bab179aeed3a5edd9
Source dataset
uspto-grants-1986_05
Patent number
US04591458

Reaction notes

Loading…