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

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Reaction Steps

To a mixture of sodium hydride (60% w/w dispersion in mineral oil) (19.24 g) and anhydrous tetrahydrofuran (450 ml) at 0° C. under a nitrogen atmosphere was added a solution of 3,4-dichlorophenylacetonitrile (89.5 g) in anhydrous tetrahydrofuran (450 ml), dropwise over 40 minutes. After a further 30 minutes, a solution of 2-(2-bromoethoxy)tetrahydropyran (100 g) in anhydrous tetrahydrofuran (100 ml) was added. The mixture was allowed to warm to room temperature and then stirred for 14 hours. 30% w/w Aqueous ammonium chloride solution (500 ml) was added and the mixture extracted with diethyl ether (2×400 ml). The organic extracts were combined, washed with water (2×400 ml), dried over anhydrous magnesium sulphate and the solvent removed under reduced pressure. The residue was chromatographed on silica gel eluting with a solvent gradient of 1:9 changing to 1:1, by volume, diethyl ether:hexane to give 2-(3,4-dichlorophenyl)-4-(tetrahydropyran-2-yloxy)-butanenitrile (51 g) as an oil and as a mixture of diastereomers.

Provenance & Evidence