Ethyl cyanoacetate → Diethyl 2-cyano-3-(p-fluorophenyl)glutarate

HRID 1016677Notes

Reaction equation

HRID 1016677 reaction equation
[C:1]([CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2].[O-]CC.[Na+].[F:13][C:14]1[CH:26]=[CH:25][C:17]([CH:18]=[CH:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:16][CH:15]=1>C(O)C>[C:1]([CH:3]([CH:18]([C:17]1[CH:16]=[CH:15][C:14]([F:13])=[CH:26][CH:25]=1)[CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2]

Participants

5

Reactant 3

HCID 7764Ethyl cyanoacetateHCID 367200Ethyl 3-(4-fluorophenyl)prop-2-enoateHCID 2723922Sodium ethoxide

Product 1

HCID 10935698Diethyl 2-cyano-3-(p-fluorophenyl)glutarateYield 47.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Procedure

To 12 g of ethyl cyanoacetate dissolved in 20 mL of ethanol, 8 g of sodium ethoxide and 40 mL of ethanol were added under cooling with ice, and then 20 g of ethyl p-fluorocinnamate and 40 mL of ethanol were added. The reaction mixture was heated under reflux for 20 hours and then filtered. The filtrate was poured into a mixture of 200 g of ice and 10 mL of concentrated hydrochloric acid and extracted with chloroform. The extract was concentrated and separated by silica gel column chromatography (hexane:ethyl acetate=9:1) to obtain 15 g of diethyl 2-cyano-3-(p-fluorophenyl)glutarate as a diastereomer mixture.

Workup

  1. temperatureunder cooling with ice
  2. temperatureThe reaction mixture was heated
  3. temperatureunder reflux for 20 hours
  4. filtrationfiltered
  5. additionThe filtrate was poured into a mixture of 200 g of ice and 10 mL of concentrated hydrochloric acid
  6. extractionextracted with chloroform
  7. concentrationThe extract was concentrated
  8. customseparated by silica gel column chromatography (hexane:ethyl acetate=9:1)

Sources & evidence

ORD record
ord-8ad2bb56f8934fcfa46549e62c074da6
Source dataset
uspto-grants-2002_11
Patent number
US06476228B1

Reaction notes

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