(2R,3S,5R)-5-[(1S,2S)-1-hydroxy-2-acetylamino-3-(3-bromo-5-fluorophenyl)-propyl]-2-(2,2-dimethylpropoxy)-3-methylmorpholine-4-carboxylic acid tert-butyl ester → HCID 68563048, 화합물

HRID 20461

반응식

HRID 20461 반응식
[Br-].[CH2:2]([Zn+])[CH2:3][CH3:4].[C:6]([O:10][C:11]([N:13]1[C@@H:18]([C@@H:19]([OH:34])[C@@H:20]([NH:30][C:31](=[O:33])[CH3:32])[CH2:21][C:22]2[CH:27]=[C:26]([F:28])[CH:25]=[C:24](Br)[CH:23]=2)[CH2:17][O:16][C@@H:15]([O:35][CH2:36][C:37]([CH3:40])([CH3:39])[CH3:38])[C@@H:14]1[CH3:41])=[O:12])([CH3:9])([CH3:8])[CH3:7]>O1CCCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:6]([O:10][C:11]([N:13]1[C@@H:18]([C@@H:19]([OH:34])[C@@H:20]([NH:30][C:31](=[O:33])[CH3:32])[CH2:21][C:22]2[CH:27]=[C:26]([F:28])[CH:25]=[C:24]([CH2:2][CH2:3][CH3:4])[CH:23]=2)[CH2:17][O:16][C@@H:15]([O:35][CH2:36][C:37]([CH3:40])([CH3:39])[CH3:38])[C@@H:14]1[CH3:41])=[O:12])([CH3:9])([CH3:8])[CH3:7]

참가 물질

5

반응물 2

HCID 68561702(2R,3S,5R)-5-[(1S,2S)-1-hydroxy-2-acetylamino-3-(3-bromo-5-fluorophenyl)-propyl]-2-(2,2-dimethylpropoxy)-3-methylmorpholine-4-carboxylic acid tert-butyl esterHCID 178455869HCID 178455869, 화합물

생성물 1

HCID 68563048HCID 68563048, 화합물수율 60%

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
65 °C

실험 절차

Add propyl zinc bromide (2.311 g) in tetrahydrofuran and (1,1′-bis(diphenylphosphino)ferrocene) palladium(II) chloride (0.015 g) to a solution of (2R,3S,5R)-5-[(1S,2S)-1-hydroxy-2-acetylamino-3-(3-bromo-5-fluorophenyl)-propyl]-2-(2,2-dimethylpropoxy)-3-methylmorpholine-4-carboxylic acid tert-butyl ester (0.07 g, 0.122 mmol) in tetrahydrofuran (1.2 mL) in a sealed tube flushed with nitrogen. Heat the tube at 65° C. for 6.5 hours. Add saturated aqueous ammonium chloride (5 mL). Extract the reaction mixture with ethyl acetate (2×30 mL). Combine the organic phases and wash with saturated aqueous sodium chloride (1×15 mL), dry over magnesium sulfate and concentrate under reduced pressure. Subject residue to silica gel chromatography, eluting with hexanes containing 15-45% ethyl acetate, to provide 0.039 g (60%) of the title compound as an off-white foam.

후처리

  1. customflushed with nitrogen
  2. extractionExtract the reaction mixture with ethyl acetate (2×30 mL)
  3. washCombine the organic phases and wash with saturated aqueous sodium chloride (1×15 mL)
  4. dry with materialdry over magnesium sulfate
  5. concentrationconcentrate under reduced pressure
  6. washSubject residue to silica gel chromatography, eluting with hexanes containing 15-45% ethyl acetate

출처 및 근거

ORD 기록
ord-a191b338a3b54ac3a0fef5aafce04a10
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07745438B2

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