3-Pyridinemethanol → 2-Fluoro-4-(3-pyridylmethoxy)benzonitrile

Participants

Reaction Conditions

Reaction Steps

A solution of triphenylphosphine (20 g) in tetrahydrofuran (300 mL) cooled at 0° C. is treated dropwise during 5 minutes with diisopropyl azodicarboxylate (15 mL) and stirred for 15 minutes at 0° C. It is then treated, dropwise, with a solution of 2-fluoro-4-hydroxybenzonitrile (7 g) and 3-pyridylmethanol (7 g) in tetrahydrofuran (200 mL) during 2 hours, and stirring is continued at ambient temperature for 18 hours. The mixture is concentrated in vacuo and the residue is dissolved in ethyl acetate (500 mL) and the solution is washed with hydrochloric acid (3×100 mL; 1 N) and the remaining organic layer is discarded. The combined acid washings are basified to pH 10 by treatment with solid sodium hydroxide and extracted with ethyl acetate (3×100 mL). This organic extract is dried over magnesium sulphate and concentrated in vacuo, and the residue is recrystallized from isopropyl ether, to give 2-fluoro-4-(3-pyridylmethoxy)benzonitrile (10 g), in the form of a white solid, m.p. 105-110° C.

Provenance & Evidence