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

HRID 1864714Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1864714
[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]

Komponenten

5

Edukt 3

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of intermediate 5B (˜0.05 M in THF) at −78° C. was added dropwise MeMgBr (3.0M 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% EtOAc in hexane) provided the title compound.

Aufarbeitung

  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% EtOAc in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-d447bb502fb04a80a149ffbc63b1e983
Quelldatensatz
uspto-grants-2009_12
Patentnummer
US07625923B2

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