Benzylamine → 2,2,2-Trifluoro-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethanamine

Participants

Reaction Steps

2,2,2-Trifluoro-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethanone (21.0 g, 81 mmol) was initially charged in diethyl ether (200 ml), and benzylamine (9.1 g, 85 mmol) and triethylamine (16.4 g, 162 mmol) were added at 0° C. Subsequently, a solution of titanium tetrachloride (7.8 g, 41 mmol) in hexane (100 ml) was added dropwise. The reaction mixture was stirred at room temperature for 3 h. The resulting suspension was filtered, and the solids were washed with diethyl ether and discarded. The solvent of the filtrate was removed under reduced pressure and the residue was taken up in triethylamine (100 ml). The solution was left to stand at room temperature for 16 h. The triethylamine was removed under reduced pressure, and the residue was taken up in dichloromethane and acidified with 10% hydrochloric acid. The mixture was stirred at room temperature for 16 h and then the phases were separated. The organic phase was washed with water and the combined aqueous phases were adjusted to pH 12 with 33% sodium hydroxide solution while cooling with ice. The aqueous phase was extracted three times with dichloromethane and the combined organic phases were dried over magnesium sulphate. The solvent was removed under reduced pressure. 6.5 g (31% of theory) of 2,2,2-trifluoro-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethanamine were obtained.

Provenance & Evidence