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

HRID 732362Notes

Reaction equation

HRID 732362 reaction equation
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]

Participants

10

Reactant 5

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

Product 1

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

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

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%).

Workup

  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)

Sources & evidence

ORD record
ord-f0673f141eee4e1480193d864ffbc8c2
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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