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

HRID 280962노트

반응식

HRID 280962 반응식
C(OC([N:11]1[CH2:16][CH2:15][CH:14]([CH2:17][CH2:18][CH2:19][CH2:20][C@@H:21]([NH:27][C@@H:28]2[C:34](=[O:35])[N:33]([CH2:36][C:37]([O:39]CC3C=CC=CC=3)=[O:38])[C:32]3[CH:47]=[CH:48][CH:49]=[CH:50][C:31]=3[O:30][CH2:29]2)[C:22]([O:24]CC)=[O:23])[CH2:13][CH2:12]1)=O)C1C=CC=CC=1>C(O)C.[C].[Pd]>[C:22]([C@H:21]([NH:27][C@@H:28]1[C:34](=[O:35])[N:33]([CH2:36][C:37]([OH:39])=[O:38])[C:32]2[CH:47]=[CH:48][CH:49]=[CH:50][C:31]=2[O:30][CH2:29]1)[CH2:20][CH2:19][CH2:18][CH2:17][CH:14]1[CH2:15][CH2:16][NH:11][CH2:12][CH2:13]1)([OH:24])=[O:23]

참가 물질

4

반응물 1

HCID 53783607benzyl 3(S)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1(R)-ethoxycarbonylpentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate

생성물 1

HCID 539058083(S)-[1(R)-carboxy-5-(4-piperidyl)pentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetic acid수율 67.8%

시약·촉매·용매 2

HCID 178418390HCID 178418390, 화합물촉매HCID 702Ethanol용매

실험 절차

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 (0.15 g) as colorless powder.

후처리

  1. custompressure until the absorption of hydrogen ceases
  2. customAfter removal of the catalyst
  3. filtrationby filtration
  4. concentrationthe filtrate is concentrated
  5. additionTo the residue is added 5N hydrogen chloride-ethyl acetate solution (1 ml)
  6. additionthe resulting mixture is diluted with ethyl ether (50 ml)
  7. dissolutionThis acid is dissolved in 1N sodium hydroxide solution (10 ml)
  8. additionAfter addition of acetic acid (2 ml)
  9. concentrationThe eluate is concentrated in vacuo

출처 및 근거

ORD 기록
ord-167956a8ae724664a97c46fbdcd128ba
출처 데이터셋
uspto-grants-1986_05
특허 번호
US04591458

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