Acetic Acid → 2-Fluoro-6-hydroxy-4-(3-thienylmethoxy)benzonitrile

Participants

Reaction Steps

A mixture of 2-fluoro-6-hydroxy-4-(3-thienylmethoxy)benzaldehyde (1 g), nitroethane (0.6 g) sodium acetate (0.66 g) and glacial acetic acid (1 mL) is heated at reflux for 2 hours. The reaction mixture is cooled to ambient temperature, water (50 mL) is added and the mixture is extracted three times with ethyl acetate (50 mL). The combined organic phases are washed with saturated brine (50 mL), dried over magnesium sulphate, filtered and concentrated under reduced pressure to leave a brown oil. The residue is purified by flash chromatography on silica eluting with a mixture of ethyl acetate and pentane (1:2 v/v). Fractions homogeneous in the required product are combined and evaporated to give 2-fluoro-6-hydroxy-4-(3-thienylmethoxy)benzonitrile (250 mg), as a yellow solid.

Provenance & Evidence