(E)-3-ethoxyprop-2-enenitrile

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To ethanol (28 ml) was added sodium (0.407 g, 17.7 mmol), and the mixture was stirred about 30 minutes. To this, (3,4-difluorophenyl)hydrazine hydrochloride (1.00 g, 5.54 mmol) and (E)-3-ethoxyacrylonitrile (0.912 ml, 8.86 mmol) were added, and the reaction was heated to reflux for 16 hours. The reaction was diluted with water (30 ml) and acidified to pH 3 with 5M hydrochloric acid. The reaction was allowed to stir at ambient temperature for another 2 hours and was then neutralized (pH 7) by the addition of 5M sodium hydroxide. The reaction was concentrated to remove most of the ethanol. The resulting suspension was extracted twice with EtOAc, and the combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel chromatography, eluting with a linear gradient of 20-100% EtOAc/hexanes to yield the desired product (0.250 g, 1.28 mmol, 23.1% yield). the reaction was heated to reflux for 16 hours to stir at ambient temperature for another 2 hours The reaction was concentrated to remove most of the ethanol The resulting suspension was extracted twice with EtOAc the combined organic layers were dried over anhydrous sodium sulfate filtered concentrated The crude product was purified by silica gel chromatography eluting with a linear gradient of 20-100% EtOAc/hexanes