Ethanol → Diethyl 2-cyano-3-(p-fluorophenyl)glutarate

HRID 1016679Notes

Reaction equation

HRID 1016679 reaction equation
[C:1]([CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2].[H-].[Na+].[F:11][C:12]1[CH:30]=[CH:29][C:15]([CH:16]=[C:17](C2C=CC=CC=2)[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:14][CH:13]=1.C(O)C>CN(C)C=O.O>[C:1]([CH:3]([CH:16]([C:15]1[CH:14]=[CH:13][C:12]([F:11])=[CH:30][CH:29]=1)[CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2]

Participants

7

Reactant 4

HCID 702EthanolHCID 7764Ethyl cyanoacetateHCID 24758Sodium hydrideHCID 70033408Ethyl p-fluorophenylcinnamate

Product 1

HCID 10935698Diethyl 2-cyano-3-(p-fluorophenyl)glutarateYield 105.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To 1 g of ethyl cyanoacetate dissolved in 5 mL of N,N-dimethylformamide, 0.5 g of sodium hydride was added under cooling with ice, and after stirring at room temperature for 30 minutes, 1.5 g of ethyl p-fluorophenylcinnamate was added. The reaction mixture was stirred at room temperature for 4 hours. After addition of ethanol under cooling with ice, the reaction mixture was poured into iced water and extracted with a solvent mixture of hexane and ethyl acetate. The extract was washed with water, and dried and concentrated. The resulting oily substance was separated by silica gel column chromatography (hexane:ethyl acetate=9:1) to obtain 1.8 g of diethyl 2-cyano-3-(p-fluorophenyl)glutarate as a diastereomer mixture.

Workup

  1. temperatureunder cooling with ice
  2. stirringThe reaction mixture was stirred at room temperature for 4 hours
  3. temperatureunder cooling with ice
  4. extractionextracted with a solvent mixture of hexane and ethyl acetate
  5. washThe extract was washed with water
  6. customdried
  7. concentrationconcentrated
  8. customThe resulting oily substance was separated by silica gel column chromatography (hexane:ethyl acetate=9:1)

Sources & evidence

ORD record
ord-87ca5cf364aa439abfc10eff3a2ce35e
Source dataset
uspto-grants-2002_11
Patent number
US06476228B1

Reaction notes

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