Benzoyl Peroxide → 5-Bromo-2-(2,2-difluoroethyl)-2,3-dihydro-1H-isoindol-1-one

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Reaction Steps

To carbon tetrachloride (160 ml) were added the compound (10.5 g, 43.2 mmol) of step A, N-bromosuccinimide (8.08 g, 45.4 mmol) and benzoyl peroxide (724 mg), and the mixture was heated under reflux for 50 min. The reaction mixture was cooled and diluted with hexane, the insoluble material was filtered off, and the obtained solution was concentrated under reduced pressure. The obtained oil (18.0 g) was dissolved in N,N-dimethylformamide (180 ml), 2,2-difluoroethylamine (5.99 g, 73.9 mmol) and triethylamine (12.0 ml, 86.1 mmol) were added, and the mixture was stirred at room temperature for 14 hr. The reaction mixture was diluted with an ethyl acetate-hexane=1:1 mixed solvent, washed with water, 10% aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the solution was concentrated under reduced pressure. The obtained oil was purified by silica gel column chromatography (ethyl acetate-hexane) to give the title compound (5.80 g, yield 49%) as a colorless oil.

Provenance & Evidence