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

HRID 1016678Notes

Reaction equation

HRID 1016678 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:24]=[CH:23][C:15]([CH:16]=[CH:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:14][CH:13]=1.C(O)C>CN(C)C=O.O.C(O)(=O)C>[C:1]([CH:3]([CH:16]([C:15]1[CH:14]=[CH:13][C:12]([F:11])=[CH:24][CH:23]=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

8

Reactant 4

HCID 702Ethanol2×HCID 7764Ethyl cyanoacetateHCID 24758Sodium hydrideHCID 367200Ethyl 3-(4-fluorophenyl)prop-2-enoate

Product 1

HCID 10935698Diethyl 2-cyano-3-(p-fluorophenyl)glutarateYield 75.5%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

12.9 g of ethyl cyanoacetate dissolved in 18 mL of N,N-dimethylformamide was added dropwise to a mixture of 4.5 g of sodium hydride and 40 mL of N,N-dimethylformamide under cooling with ice, and after 1.5 hours of stirring at room temperature, a solution of 20 g of ethyl p-fluorocinnamate in 18 mL of N,N-dimethylformamide was added. The mixture was heated at 50 to 60° C. for 21 hours. 30 mL of absolute ethanol was added under cooling with ice, and then an ethanol solution of acetic acid was added. After addition of water, the reaction mixture was extracted with ethyl acetate, and the extract was dried, concentrated and separated by silica gel column chromatography (hexane:ethyl acetate=5:1) to obtain 23.9 g of diethyl 2-cyano-3-(p-fluorophenyl)glutarate as a diastereomer mixture.

Workup

  1. temperatureunder cooling with ice
  2. temperatureThe mixture was heated at 50 to 60° C. for 21 hours
  3. temperatureunder cooling with ice
  4. extractionthe reaction mixture was extracted with ethyl acetate
  5. customthe extract was dried
  6. concentrationconcentrated
  7. customseparated by silica gel column chromatography (hexane:ethyl acetate=5:1)

Sources & evidence

ORD record
ord-8a946945f5fc4321bebbf96a7404be9f
Source dataset
uspto-grants-2002_11
Patent number
US06476228B1

Reaction notes

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