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

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence