Sodium hydride → 2-[2-chloro-4-(pyrrolidine-1-carbonyl)benzyl]-3-oxopentanoic Acid Ethyl Ester

HRID 2266620Notes

Reaction equation

HRID 2266620 reaction equation
[CH2:1]([O:3][C:4](=[O:10])[CH2:5][C:6](=[O:9])[CH2:7][CH3:8])[CH3:2].[H-].[Na+].Br[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([N:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)=[O:22])=[CH:17][C:16]=1[Cl:28]>COCCOC.CN(C)C=O.[Cl-].[NH4+]>[CH2:1]([O:3][C:4](=[O:10])[CH:5]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([N:23]2[CH2:24][CH2:25][CH2:26][CH2:27]2)=[O:22])=[CH:17][C:16]=1[Cl:28])[C:6](=[O:9])[CH2:7][CH3:8])[CH3:2]

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 78656Ethyl 3-oxovalerateHCID 68783266(4-Bromomethyl-3-chlorophenyl)pyrrolidin-1-ylmethanone

Product 1

HCID 687846752-[2-chloro-4-(pyrrolidine-1-carbonyl)benzyl]-3-oxopentanoic Acid Ethyl Ester

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent3×HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-oxopentanoic acid ethyl ester (14 mL) in 1,2-dimethoxyethane (25 mL) was added to a stirred suspension of sodium hydride (60% in oil, 3.7 g) in 1,2-dimethoxyethane (250 mL) and N,N-dimethylformamide (30 mL) at 0° C. and the resulting mixture was stirred at 0° C. for 10 minutes. A solution of (4-bromomethyl-3-chlorophenyl)pyrrolidin-1-ylmethanone (9.7 g) in 1,2-dimethoxyethane (25 mL) was added and the resulting mixture warmed to room temperature and then stirred at this temperature for 20 hours. The mixture was diluted with saturated aqueous ammonium chloride solution, extracted with diethyl ether and the combined extracts washed with saturated aqueous sodium chloride solution and then dried over magnesium sulfate. The solvent was removed under reduced pressure and the residue purified by column chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (9:1 by volume) to afford title compound, 1.8 g.

Workup

  1. temperaturethe resulting mixture warmed to room temperature
  2. stirringstirred at this temperature for 20 hours
  3. extractionextracted with diethyl ether
  4. washthe combined extracts washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. customThe solvent was removed under reduced pressure
  7. customthe residue purified by column chromatography on silica gel
  8. washeluting with a mixture of cyclohexane and ethyl acetate (9:1 by volume)

Sources & evidence

ORD record
ord-1b89f174776242f6ae715357ec91880a
Source dataset
uspto-grants-2010_12
Patent number
US07858640B2

Reaction notes

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