Acetic Acid → (2S,4S)-4-acetoxy-1-tert-butoxycarbonyl-2-pyrrolidinemethanol

HRID 354425Notes

Reaction equation

HRID 354425 reaction equation
[C:1]([O:4][C@@H:5]1[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:7]([CH2:17][O:18][Si](C(C)(C)C)(C2C=CC=CC=2)C2C=CC=CC=2)[CH2:6]1)(=[O:3])[CH3:2].C(O)(=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[C:1]([O:4][C@@H:5]1[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:15])([CH3:14])[CH3:16])=[O:11])[C@H:7]([CH2:17][OH:18])[CH2:6]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 2724141Tetrabutylammonium FluorideHCID 69340895(2S,4S)4-acetoxy-1-tert-butoxycarbonyl-2-tert-butyldiphenylsilyloxymethypyrrolidine

Product 1

HCID 69332993(2S,4S)-4-acetoxy-1-tert-butoxycarbonyl-2-pyrrolidinemethanolYield 79.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of (2S,4S)-4-acetoxy-1-tert-butoxycarbonyl-2-tert-butyldiphenylsilyloxymethypyrrolidine (23.3 g, 46.9 mmol) and acetic acid (6.0 ml, 104.8 mmol) in THF (470 ml) was added TBAF (93.8 ml, 93.8 mmol) at 0° C. After 24 h stirring, the mixture was concentrated in vacuo. The resulting residue was diluted with EtOAC and aq. NH4Cl and extracted with EtOAc. The combined extracts were washed with brine, which were dried over Na2SO4 and concntrated in vacuo. The residue was chromatographed on silica gel (700 g, CHCl3/EtOAc (4/1)], to give (2S,4S)-4-acetoxy-1-tert-butoxycarbonyl-2-pyrrolidinemethanol (9.70 g, 8%) as a colorless oil. 1H-NMR (CDCl3) δ1.47 (s, 9H), 1.63 (m, 1H), 1.81 (m, 1H), 2.07 (s, 3H), 234 (m, 1H), 3.42 (dd, J=12.7, 0.9 Hz, 1H), 3.62-3.85 (m, 3H), 4.48 (br, 1H), 5.20 (br, 1H).

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. additionThe resulting residue was diluted with EtOAC and aq. NH4Cl
  3. extractionextracted with EtOAc
  4. washThe combined extracts were washed with brine, which
  5. dry with materialwere dried over Na2SO4
  6. customThe residue was chromatographed on silica gel (700 g, CHCl3/EtOAc (4/1)],

Sources & evidence

ORD record
ord-f0c6640ccda3407f99f24e9b6f48e8c5
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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