1H-Imidazole-4-carbaldehyde → (2R,4R)-1-allyloxycarbonyl-4-t-butyldimethylsilyloxy-2-{2-(5-formylimidazol-1-yl)ethyl}pyrrolidine

HRID 975714Notes

Reaction equation

HRID 975714 reaction equation
[CH2:1]([O:4][C:5]([N:7]1[CH2:11][C@H:10]([O:12][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])[CH2:9][C@H:8]1[CH2:20][CH2:21]OS(C)(=O)=O)=[O:6])[CH:2]=[CH2:3].[CH:27]([C:29]1[N:30]=[CH:31][NH:32][CH:33]=1)=[O:28].CC(C)([O-])C.[K+]>CN(C)C=O.C(OCC)(=O)C.O>[CH2:1]([O:4][C:5]([N:7]1[CH2:11][C@H:10]([O:12][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:14])[CH3:15])[CH2:9][C@H:8]1[CH2:20][CH2:21][N:30]1[C:29]([CH:27]=[O:28])=[CH:33][N:32]=[CH:31]1)=[O:6])[CH:2]=[CH2:3]

Participants

7

Reactant 3

HCID 764281H-Imidazole-4-carbaldehydeHCID 15537961(2R,4R)-1-allyloxycarbonyl-2-(2-methanesulfonyloxyethyl)-4-(t-butyldimethylsilyloxy)pyrrolidineHCID 23665647Potassium tert-butoxide

Product 1

HCID 54006383(2R,4R)-1-allyloxycarbonyl-4-t-butyldimethylsilyloxy-2-{2-(5-formylimidazol-1-yl)ethyl}pyrrolidineYield 23.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of (2R,4R)-1-allyloxycarbonyl-4-tert-butyldimethylsilyloxy-2-(2-methanesulfonyloxyethyl)pyrrolidine (63 g) and 4-formylimidazole (17.8 g) in N,N-dimethylformamide (300 ml) was added potassium tert-butoxide (20.8 g) by portions. Then, the mixture was stirred at 45° C. for 2 hours. Evaporation of the solvent gave a residue, which was dissolved in a mixture of ethyl acetate (1.5 l) and water (200 ml). The organic layer was separated, washed in turn with 1N hydrochloric acid (100 ml) and brine (300 ml×3), and dried over magnesium sulfate. Evaporation of the solvent gave an oil, which was chromatographed on silica gel (2 l) eluting with a mixture of hexane and ethyl acetate (1:1 to 1:2 to 0:1). The former active fractions were collected and concentrated in vacuo to give (2R,4R)-1-allyloxycarbonyl-4-tert-butyldimethylsilyloxy-2-{2-(5-formylimidazol-1-yl)ethyl}pyrrolidine (14.9 g).

Workup

  1. customEvaporation of the solvent
  2. customgave a residue, which
  3. customThe organic layer was separated
  4. washwashed in turn with 1N hydrochloric acid (100 ml) and brine (300 ml×3)
  5. dry with materialdried over magnesium sulfate
  6. customEvaporation of the solvent
  7. customgave an oil, which
  8. customwas chromatographed on silica gel (2 l)
  9. washeluting with a mixture of hexane and ethyl acetate (1:1 to 1:2 to 0:1)
  10. customThe former active fractions were collected
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1298884a8f0b46a480ca6300e84bafc2
Source dataset
uspto-grants-1997_03
Patent number
US05608056

Reaction notes

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