Sodium hydride → 2-(3-Cyano-3-(3,4-dichlorophenyl)propyl)oxytetrahydropyran

Participants

Reaction Steps

To a mixture of 60% w/w sodium hydride dispersion in oil (19.24 g, 1.05 mol. equiv.) in dry tetrahydrofuran (450 ml) at 0° C. under nitrogen was added a solution of 3,4-dichlorophenylacetonitrile (89.5 g, 1 mol. equiv.) in dry tetrahydrofuran (450 ml), dropwise over forty minutes. After a further thirty minutes, a solution of 2-bromoethoxytetrahydropyran (100 g , 1 mol. equiv.) in tetrahydrofuran (100 ml) was added and the mixture allowed to warm to room temperature and stirred for fourteen hours. 30% Aqueous ammonium chloride solution (500 ml) was added and the mixture extracted with diethyl ether (2×400 ml). The organic layers were combined and washed with water (2×400 ml), dried over magnesium sulphate, and the solvent removed under reduced pressure. The residue was then chromatographed using silica gel eluting with a solvent gradient of diethyl ether:hexane (1:9 to 1:1, by volume) to give the title compound (51 g). TLC Rf =0.55 (silica, methyl tert-butyl ether:hexane, 1:1, by volume). LRMS m/z=333 (m+NH4)+.

Provenance & Evidence