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

HRID 1162507노트

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HRID 1162507 반응식
[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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

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온도
-78 °C

실험 절차

To a solution of intermediate 7B (˜0.05 M in THF) at −78° C. was added dropwise MeMgBr (3.OM in Et2O, 3 eq). 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 eq) at −78° C. Warm to RT, dilute with EtOAc and wash with a 1: 1 mixture of sat. aq. NaHCO3 and sat aq. NaCl. Back extract aqueous layer. Combine organic extracts, dry over MgSO4, filter and concentrate. Purification by flash chromatography (silica gel, step gradient 0-10-20% ethylacetate in hexane) provided the title compound.

후처리

  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 sat. aq. NaHCO3
  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% ethylacetate in hexane)

출처 및 근거

ORD 기록
ord-493dadb924ec4f0499416bf044dcd849
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07820702B2

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