Citric Acid → (2S,3R)-3-([(1S)-2,2-Dimethyl-1-([(1R)-1-phenylethyl]aminocarbonyl)propyl]aminocarbonyl)-2ethoxy-6-(3-fluoro-4-phenoxyphenyl)hexanoic acid

HRID 1700983노트

반응식

HRID 1700983 반응식
O.[OH-].[Li+].[CH3:4][C:5]([CH3:48])([CH3:47])[C@H:6]([NH:18][C:19]([C@H:21]([CH2:30][CH2:31][CH2:32][C:33]1[CH:38]=[CH:37][C:36]([O:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[C:35]([F:46])[CH:34]=1)[C@H:22]([O:27][CH2:28][CH3:29])[C:23]([O:25]C)=[O:24])=[O:20])[C:7]([NH:9][C@@H:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH3:11])=[O:8].O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CO>[CH3:48][C:5]([CH3:4])([CH3:47])[C@H:6]([NH:18][C:19]([C@H:21]([CH2:30][CH2:31][CH2:32][C:33]1[CH:38]=[CH:37][C:36]([O:39][C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)=[C:35]([F:46])[CH:34]=1)[C@H:22]([O:27][CH2:28][CH3:29])[C:23]([OH:25])=[O:24])=[O:20])[C:7]([NH:9][C@@H:10]([C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[CH3:11])=[O:8]

참가 물질

6

반응물 4

HCID 311Citric AcidHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 57064299methyl (2S,3R)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)-2-ethoxy-6-(3-fluoro-4-phenoxyphenyl)hexanoate

생성물 1

HCID 22950018(2S,3R)-3-([(1S)-2,2-Dimethyl-1-([(1R)-1-phenylethyl]aminocarbonyl)propyl]aminocarbonyl)-2ethoxy-6-(3-fluoro-4-phenoxyphenyl)hexanoic acid수율 18.1%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

Lithium hydroxide hydrate (116 mg, 2.83 mmol) was added to a solution of methyl (2S,3R)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)-2-ethoxy-6-(3-fluoro-4-phenoxyphenyl)hexanoate (368 mg, 0.566 mmol) in methanol:water=10:1 (5 mL) and the mixture was stirred at room temperature for 2 h. The solution was neutralised with 5% aqueous citric acid and concentrated under reduced pressure. The residue was partitioned between ethyl acetate (100 mL) and 5% aqueous citric acid (20 mL), washed with saturated aqueous sodium chloride (20 mL), dried MgSO4), and concentrated under reduced pressure. Purification by flash chromatography (eluting with dichloromethane:methanol=20:1 to 10:1) gave the title compound (62 mg, 18%) as a colourless glass, and some mixed fractions. These were combined and repurified by flash chromatography (eluting with ethyl acetate:hexane:acetic acid=33:66:1 to 50:50:1) to give the title compound (37 mg, 11%), as a white solid.

후처리

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was partitioned between ethyl acetate (100 mL) and 5% aqueous citric acid (20 mL)
  3. washwashed with saturated aqueous sodium chloride (20 mL), dried MgSO4), and
  4. concentrationconcentrated under reduced pressure
  5. customPurification
  6. washby flash chromatography (eluting with dichloromethane:methanol=20:1 to 10:1)

출처 및 근거

ORD 기록
ord-430eb4ab388c4d1bb00ef5df9301dfa8
출처 데이터셋
uspto-grants-2002_02
특허 번호
US06350907B1

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