Imidazole → tert-butyl(3S)-3-{[tert-butyl(dimethyl)silyloxy]methyl}-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate

HRID 1510388Notes

Reaction equation

HRID 1510388 reaction equation
[OH:1][CH2:2][C@:3]1([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:7][C:6](=[O:8])[N:5]([C@@H:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH3:10])[CH2:4]1.N1C=CN=C1.[Si:29](Cl)([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30].[Cl-].[NH4+]>CN(C)C=O>[Si:29]([O:1][CH2:2][C@:3]1([C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[CH2:7][C:6](=[O:8])[N:5]([C@@H:9]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH3:10])[CH2:4]1)([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 25517Ammonium ChlorideHCID 28928tert-Butyldimethylsilyl chlorideHCID 57758657HCID 57758657, compound

Product 1

HCID 57758663tert-butyl(3S)-3-{[tert-butyl(dimethyl)silyloxy]methyl}-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylateYield 71.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl (3S)-3-hydroxymethyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate (8.23 g, 25.8 mmol) and imidazole (2.63 g, 38.7 mmol) in N,N-dimethylformamide (150 mL), tert-butyl dimethylsilyl chloride (4.66 g, 31.0 mmol) was added in an ice bath, and the mixture was stirred at room temperature for 4 hours. To the reaction mixture, saturated aqueous solution of ammonium chloride (300 mL) was added in an ice bath, and the mixture was extracted with diethylether (300 mL×2). The organic layer was washed with water (300 mL×2) and saturated aqueous solution of sodium chloride (200 mL), and dried with anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (elusion by hexane:ethyl acetate, 10:1→1:1) to obtain 7.98 g (71%) of the title compound as a colorless oily substance.

Workup

  1. extractionthe mixture was extracted with diethylether (300 mL×2)
  2. washThe organic layer was washed with water (300 mL×2) and saturated aqueous solution of sodium chloride (200 mL)
  3. dry with materialdried with anhydrous magnesium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (elusion by hexane:ethyl acetate, 10:1→1:1)

Sources & evidence

ORD record
ord-dd4f018cfcc642588e61352b873a8db5
Source dataset
uspto-grants-2012_07
Patent number
US08211910B2

Reaction notes

Loading…