Triethylamine → 1-(3,4-Dichloro-benzyl)-azetidine-3-carbonitrile

Participants

Reaction Steps

A solution of 1-Benzhydryl-azetidine-3-carbonitrile (0.25 g, 1.0 mmol) in dichloromethane (2 ml) is treated with 1-chloroethylchloroformate (0.12 ml, 1.1 mmol). The reaction mixture is stirred at room temperature for 3 hours, the solvent evaporated and the residue taken-up in methanol and refluxed for 1 hour. The reaction mixture is cooled to room temperature and stirred for a further 18 hours. The solvent is evaporated to afford crude azetidine-3-carbonitrile hydrochloride. The crude azetidine-3-carbonitrile is dissolved in dichloromethane (3 ml) and treated with triethylamine (0.25 ml, 2.0 mmol) and 3,4-dichlorobenzylbromide (0.24 g, 1.0 mmol). The reaction mixture is stirred at ambient temperature for 2 hours, then washed with water, the organic phase dried over magnesium sulphate and evaporated. The crude product is purified by chromatography over flash silica using hexane:ethylacetate 2:1 as eluent to afford 1-(3,4-Dichloro-benzyl)-azetidine-3-carbonitrile. [MH]+ 240.97

Provenance & Evidence