(2S,3S)-tert-Butyl 3-((tert-butyldimethylsilyl)oxy)-2-formylpyrrolidine-1-carboxylate → (2S,3S)-N-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-((1R)-1-hydroxyethyl)pyrrolidine

HRID 501651Notes

Reaction equation

HRID 501651 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]COC(C)=O.CCCCCC>C1COCC1>[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[C@H:21]([OH:22])[CH3:26])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 16731848(2S,3S)-tert-Butyl 3-((tert-butyldimethylsilyl)oxy)-2-formylpyrrolidine-1-carboxylateHCID 21226206Ethyl acetate hexaneHCID 178418689HCID 178418689, compound

Product 1

HCID 68459657(2S,3S)-N-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-((1R)-1-hydroxyethyl)pyrrolidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of intermediate (2S,3S)—N-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-formylpyrrolidine (4.7 g, 14.26 mmol) in THF (70 mL) at −78° C. was added dropwise MeMgBr (3.0 M in THF, 23.8 mmol). The reaction was stirred at −78° C. for 3 h and TLC (20% EtOAc/hexane) showed complete reaction. The reaction was quenched by the addition of HOAc (5.0 mL) at −78° C., warmed to rt and diluted with EtOAc (20 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (2×30 mL). The combined organic layers were washed with saturated NaHCO3 solution and brine, dried (MgSO4), filtered and concentrated to give the crude product. Purification by flash chromatography (120 g ISCO silica gel column, 0-30% EtOAc/hexane) provided 80A-a (760 mg) and 80A-b (1.54 g) as colorless oil. 80A-a: For (20% EtOAc/hexane) 0.29. 80A-b: For (20% EtOAc/hexane) 0.25.

Workup

  1. customreaction
  2. customThe reaction was quenched by the addition of HOAc (5.0 mL) at −78° C.
  3. temperaturewarmed to rt
  4. additiondiluted with EtOAc (20 mL)
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with EtOAc (2×30 mL)
  7. washThe combined organic layers were washed with saturated NaHCO3 solution and brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give the crude product
  12. customPurification by flash chromatography (120 g ISCO silica gel column, 0-30% EtOAc/hexane)

Sources & evidence

ORD record
ord-cdf6c6b5c30b4bfeb3164ebec17ccb95
Source dataset
uspto-grants-2010_08
Patent number
US07772267B2

Reaction notes

Loading…