Acetic Acid → (2R,3S)-N-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-(1-hydroxyethyl)pyrrolidine

HRID 132686Notes

Reaction equation

HRID 132686 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[CH:21]=[O:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Mg+].[Br-].[CH3:26]C(O)=O>CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[CH:21]([OH:22])[CH3:26])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 16731848(2S,3S)-tert-Butyl 3-((tert-butyldimethylsilyl)oxy)-2-formylpyrrolidine-1-carboxylateHCID 178418689HCID 178418689, compound

Product 1

HCID 59734597(2R,3S)-N-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-(1-hydroxyethyl)pyrrolidine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 1J (˜0.05 M in THF) at −78° C. was added dropwise MeMgBr (3.0M in Et2O, 3 equiv). The reaction was stirred at −78° C. for 1.5-2 h (quench small aliquot in 10% MeOH/DCM, spot TLC-silica gel, 30% EtOAc/Hex-stain with 5% HCl/MeOH, heat and then ninhydrin, heat). Quench reaction by addition of HOAc (3 equiv) at −78° C. Warm to rt, dilute with EtOAc and wash with a 1:1 mixture of saturated aq. NaHCO3 and brine. Back extract aqueous layer. Combine organic extracts, dry over MgSO4, filter and concentrate. Purification by flash chromatography (silica gel, step gradient 0-10-20% EtOAc in hexane) provided the title compound.

Workup

  1. customquench small aliquot in 10% MeOH/DCM
  2. temperaturespot TLC-silica gel, 30% EtOAc/Hex-stain with 5% HCl/MeOH, heat
  3. temperatureninhydrin, heat)
  4. customQuench
  5. customreaction
  6. temperatureWarm to rt
  7. washwash with a 1:1 mixture of saturated aq. NaHCO3 and brine
  8. extractionBack extract aqueous layer
  9. dry with materialCombine organic extracts, dry over MgSO4
  10. filtrationfilter
  11. concentrationconcentrate
  12. customPurification by flash chromatography (silica gel, step gradient 0-10-20% EtOAc in hexane)

Sources & evidence

ORD record
ord-fd3d53bcea014a9fb7673c6bdd38efa9
Source dataset
uspto-grants-2008_06
Patent number
US07388027B2

Reaction notes

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