Hydrogen Peroxide → 2-(R)-[2-(S)-Azidocarbonyl-1-(S)-(tert-butyl-dimethylsilanyloxy)-3-phenylpropyl]-4-(R)-fluoropyrrolidine-1-carboxylic acid tert-butyl ester

HRID 732362노트

반응식

HRID 732362 반응식
OO.[C:3]([O:7][C:8]([N:10]1[CH2:14][C@H:13]([F:15])[CH2:12][C@@H:11]1[C@@H:16]([O:36][Si:37]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38])[C@H:17]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:18]([N:20]1[C@@H](C(C)C)COC1=O)=[O:19])=[O:9])([CH3:6])([CH3:5])[CH3:4].[OH-].[Li+].C(N(C(C)C)CC)(C)C.C1(P([N:69]=[N+:70]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1>C1COCC1.C(OCC)(=O)C.ClCCl.CO>[C:3]([O:7][C:8]([N:10]1[CH2:14][C@H:13]([F:15])[CH2:12][C@@H:11]1[C@@H:16]([O:36][Si:37]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38])[C@@H:17]([C:18]([N:20]=[N+:69]=[N-:70])=[O:19])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4]

참가 물질

10

반응물 5

HCID 784Hydrogen PeroxideHCID 3939Lithium HydroxideHCID 81531Diisopropylethylamine2회HCID 199401P,P-Diphenylphosphinic azide2회HCID 68815846HCID 68815846, 화합물

생성물 1

HCID 866149952-(R)-[2-(S)-Azidocarbonyl-1-(S)-(tert-butyl-dimethylsilanyloxy)-3-phenylpropyl]-4-(R)-fluoropyrrolidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 4

HCID 887Methanol용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

Add an aqueous solution of hydrogen peroxide (30% solution, 2.7 mL, 28.1 mmol) dropwise to a solution of 2-(R)-[2-(S)-benzyl-1-(S)-(tert-butyl-dimethylsilanyloxy)-3-(4-(S)-isopropyl-2-oxo-oxazolidin-3-yl)-3-oxopropyl]-4-(R)-fluoropyrrolidine-1-carboxylic acid tert-butyl ester (2.779 g, 4.69 mmol) in THF (15 mL) at 0° C. Add 2 N lithium hydroxide (4.7 mL, 9.38 mmol) dropwise, stir 60 min and warm to room temperature. Add methanol (5 mL) and stir 18 h. Dilute with ethyl acetate and wash with 1 N HCl, saturated aqueous sodium chloride, dry (magnesium sulfate) and concentrate. Dissolve residue in dichloromethane (30 mL) and add diisopropylethylamine (1.2 mL, 7.03 mmol) followed by diphenylphosphoryl azide (1.1 mL, 5.16 mmol). Stir 1 h and add diisopropylethylamine (1.2 mL, 7.03 mmol) followed by diphenylphosphoryl azide (1.1 mL, 5.16 mmol). Stir 3.5 h, concentrate and purify (silica gel chromatography, eluting with hexanes and ethyl acetate) to give the title compound as a residue (0.79 g, 32%).

후처리

  1. washwash with 1 N HCl, saturated aqueous sodium chloride
  2. dry with materialdry (magnesium sulfate)
  3. concentrationconcentrate
  4. stirringStir 1 h
  5. stirringStir 3.5 h
  6. concentrationconcentrate
  7. custompurify
  8. wash(silica gel chromatography, eluting with hexanes and ethyl acetate)

출처 및 근거

ORD 기록
ord-f0673f141eee4e1480193d864ffbc8c2
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07585885B2

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