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

HRID 732362Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 732362
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]

Komponenten

10

Edukt 5

HCID 784Hydrogen PeroxideHCID 3939Lithium HydroxideHCID 81531Diisopropylethylamine2×HCID 199401P,P-Diphenylphosphinic azide2×HCID 68815846HCID 68815846, Verbindung

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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%).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-f0673f141eee4e1480193d864ffbc8c2
Quelldatensatz
uspto-grants-2009_09
Patentnummer
US07585885B2

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