Imidazole → (3S)-3-[3-(tert-Butyldimethylsilyloxy)-1-propyl]-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester

HRID 1917334Notes

Reaction equation

HRID 1917334 reaction equation
[C:1]([O:5][C:6]([C@@:8]1([CH2:22][CH2:23][CH2:24][OH:25])[CH2:12][C:11](=[O:13])[N:10]([C@@H:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH3:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CN=C1.[Si:31](Cl)([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32]>CN(C)C=O>[C:1]([O:5][C:6]([C@@:8]1([CH2:22][CH2:23][CH2:24][O:25][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[CH2:12][C:11](=[O:13])[N:10]([C@@H:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH3:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 67491012(3S)-3-(3-hydroxy-1-propyl)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester

Product 1

HCID 67490948(3S)-3-[3-(tert-Butyldimethylsilyloxy)-1-propyl]-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl esterYield 48.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(3S)-3-(3-Hydroxy-1-propyl)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester (46 g) and imidazole (11.9 g) were dissolved in dimethylformamide (600 mL). After addition of tert-butyldimethylsilyl chloride (23.2 g) under ice-cooling, the mixture was stirred at room temperature for 59.5 hours. The reaction solution was extracted with a 10% citric acid solution and ethyl acetate. Then, the organic layer was sequentially washed with saturated sodium bicarbonate water and brine, dried over anhydrous sodium sulfate, and filtered. Thereafter, the solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography (hexane:ethyl acetate=9:1→8:2→2:1) to give 29.7 g of the title compound as a pale yellow oil.

Workup

  1. temperaturecooling
  2. extractionThe reaction solution was extracted with a 10% citric acid solution and ethyl acetate
  3. washThen, the organic layer was sequentially washed with saturated sodium bicarbonate water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customThereafter, the solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-6ca62e31424241bbabbacb1fc092439d
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

Loading…