2-Iodo-4-(trifluoromethyl)aniline → 4-Amino-3-cyanobenzotrifluoride

Participants

Reaction Conditions

Reaction Steps

In a 2-liter flask equipped with a septum inlet, magnetic stirring bar, and condenser leading to a mercury bubbler was placed 100 g (0.348 mol) of 4-amino-3-iodobenzotrifluoride in 1 liter DMF. To this reaction flask with stirring was added 37.4 g (0.416 mol) of copper cyanide and the contents were heated to 100° C. under nitrogen for fourteen hours. Afterwards, TLC analysis revealed minor starting material (20/80) ethyl acetate/hexane. The contents were cooled to 40° C. and filtered through a pad of Celite. The solids were washed with ether and the filtrate transferred to a separatory funnel and washed with about 5% aqueous ammonium hydroxide. The aqueous layer was back-extracted with ether and the organics were combined and washed with brine, dried over magnesium sulfate, filtered and concentrated to yield a black oil. The oil was chromatographed on a Biotage 75L cartridge with ethyl acetate/hexane to obtain 68 g 2-amino-5-(trifluoromethyl)benzonitrile as a black solid.

Provenance & Evidence