Diethyl Ether → 2-(4-Chlorophenyl)-1-[1-(3,4-dichlorophenyl)cyclobutyl]ethanone

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Reaction Steps

A solution of 1-(3,4-dichlorophenyl)cyclobutanecarbonitrile (6.56 g) in toluene (100 ml) was added dropwise under nitrogen to a stirred solution of 4-chlorobenzylmagnesium chloride [prepared in the usual manner from 4-chlorobenzyl chloride (9.07) and magnesium (1.08 g)] in ether (100 ml). When the addition was complete, ether was distilled from the mixture until the internal temperature rose to 95° C., then the mixture was stirred at this temperature for 19 h, cooled to ambient temperature, and quenched by the dropwise addition of water (50 ml) followed by concentrated hydrochloric acid (10 ml). The mixture was stirred at 95° C. for 3 hours, then it was cooled to ambient temperature. The organic phase was separated, washed with water (100 ml) and saturated brine (100 ml), dried (Na2SO4), and the solvent was removed in vacuo. The residue was purified via flash chromatography over silica using 1:9-1:4 mixtures of ethyl acetate and petroleum ether (b.p. 60-80° C.) as eluant. Appropriate fractions were combined and the solvents removed in vacuo to give 2-(4-chlorophenyl)-1-[1-(3,4-dichlorophenyl)cyclobutyl]ethanone as a yellow oil (7.51 g) which solidified slowly at ambient temperature to give a yellow solid, m.p. 82-84° C.

Provenance & Evidence