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

HRID 2296765Notes

Reaction equation

[C:1]([CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2].[F:9][C:10]1[CH:22]=[CH:21][C:13]([CH:14]=[CH:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:12][CH:11]=1.[O-]CC.[Na+]>C(O)(=O)C>[C:1]([CH:3]([CH:14]([C:13]1[CH:12]=[CH:11][C:10]([F:9])=[CH:22][CH:21]=1)[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2]

Participants

Conditions

Temperature: 5 °C

Procedure

A mixture of ethyl cyanoacetate (13.56 g) and ethyl 4-fluorocinnamate (19.4 g) was added to a solution of sodium ethoxide (2.3 g sodium in 50 ml ethanol) at 60° C. over 2-3 minutes and the mixture heated under reflux for 1 hour then cooled to 5° C. Glacial acetic acid (6 ml) was added slowly to the reaction mixture at below 5° C. The bulk of the ethanol was removed by distillation at reduced pressure the residue diluted with water (40 ml), extracted with toluene (3×30 ml), and the combined organic phases dried over anhydrous magnesium sulphate. The solution was filtered, evaporated to an oil (28.6 g), and distilled at 166-180° C. at 3.5 mbar to produce diethyl 2-cyano-3-(4-fluorophenyl)-glutarate (23 g, 74% yield, 98% purity).

Workup

temperaturethe mixture heated
temperatureunder reflux for 1 hour
customThe bulk of the ethanol was removed by distillation at reduced pressure the residue
additiondiluted with water (40 ml)
extractionextracted with toluene (3×30 ml)
dry with materialthe combined organic phases dried over anhydrous magnesium sulphate
filtrationThe solution was filtered
customevaporated to an oil (28.6 g)
distillationdistilled at 166-180° C. at 3.5 mbar

Sources & evidence

ORD record: ord-7108f7573a1949c691a1590db6481c9e
Source dataset: uspto-grants-2002_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06489347B1

Reaction notes

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