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

HRID 350488Notes

Reaction equation

HRID 350488 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@@:7]([CH2:21][O:22][SiH3])(C(C)(C)C)[C:6]1(C1C=CC=CC=1)C1C=CC=CC=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]([CH2:21][OH:22])[CH2:6]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 2724141Tetrabutylammonium FluorideHCID 131726275(2S,4S)-4-acetoxy-1-tert-butoxycarbonyl-2-tertbutyldiphenyl silyloxy methypyrrolidine

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-butyldiphenyl silyloxy methypyrrolidine (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 concentrated 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) δ 1.47 (s, 9H), 1.63 (m, 1H), 1.81 (m, 1H), 2.07 (s, 3H), 2.34 (m, 1H), 3.42 (dd, J=12.7, 0.9 Hz, 1H), 3.62–3.85 (m, 31H), 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. concentrationconcentrated in vacuo
  7. customThe residue was chromatographed on silica gel [700 g, CHCl3/EtOAc (4/1)]

Sources & evidence

ORD record
ord-6fe3cca5d3d745b0956016e655d65e23
Source dataset
uspto-grants-2007_02
Patent number
US07179819B2

Reaction notes

Loading…