Citric Acid → 3-Ethyl-1-(4-fluorobenzoyl)-2-oxopyrrolidine-3-carbonitrile

HRID 632772Notes

Reaction equation

HRID 632772 reaction equation
[F:1][C:2]1[CH:17]=[CH:16][C:5]([C:6]([N:8]2[CH2:12][CH2:11][CH:10]([C:13]#[N:14])[C:9]2=[O:15])=[O:7])=[CH:4][CH:3]=1.[H-].[Na+].I[CH2:21][CH3:22].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[CH2:21]([C:10]1([C:13]#[N:14])[CH2:11][CH2:12][N:8]([C:6](=[O:7])[C:5]2[CH:16]=[CH:17][C:2]([F:1])=[CH:3][CH:4]=2)[C:9]1=[O:15])[CH3:22]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 6340IodoethaneHCID 24758Sodium hydrideHCID 114361891-(4-Fluorobenzoyl)-2-oxo-3-pyrrolidinecarbonitrile

Product 1

HCID 1178403873-Ethyl-1-(4-fluorobenzoyl)-2-oxopyrrolidine-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-fluorobenzoyl)-2-oxopyrrolidine-3-carbonitrile (25 g) in DMF (215 mL) was added a sodium hydride 60% dispersion in mineral oil (6.5 g) under ice-cooling. The reaction mixture was stirred under ice-cooling for 1 hr, and iodoethane (17 mL) was added slowly thereto. The reaction mixture was stirred under ice-cooling for 2 hr, and poured into 10% aqueous citric acid solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (23 g).

Workup

  1. temperaturecooling
  2. temperaturecooling for 1 hr
  3. stirringThe reaction mixture was stirred under ice-
  4. temperaturecooling for 2 hr
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe extract was washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-1fbcf10ff0564956bdba5c5b4001e5eb
Source dataset
uspto-grants-2016_04
Patent number
US09321757B2

Reaction notes

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