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

HRID 446115Notes

Reaction equation

HRID 446115 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-c81c4b04414a40a88fe8cddd6d657bed
Source dataset
uspto-grants-2013_07
Patent number
US08476429B2

Reaction notes

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