1-Bromo-2-chloro-4-fluorobenzene → 2-(2-Chloro-4-fluorobenzoyl)cyclopropanecarbonitrile

Participants

Reaction Steps

A solution of 24.0 g (115 mmol) of 2-chloro-4-fluorobromobenzene in 20 ml of diethyl ether was added dropwise to 2.92 g (120 mmol) of magnesium turnings in 780 ml of diethyl ether, activated by adding a few drops of dibromoethane, and the reaction mixture was heated under reflux overnight. The reaction solution was added dropwise under argon to a solution of 17.7 g (68.8 mmol) of the compound from Example 73A in 300 ml of THF, and the reaction mixture was stirred initially at RT overnight and then under reflux for 8 h. It was concentrated and taken up in ethyl acetate and saturated aqueous ammonium chloride solution, the phases were separated, and the organic phase was washed with water and saturated aqueous sodium bicarbonate solution, dried over magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica gel (mobile phase: toluene/ethyl acetate gradient) to result in 2.20 g (14% of theory) of the title compound.

Provenance & Evidence