Triethylamine → N-[(6-chloro-5-fluoropyridin-3-yl)methyl]-2,2-difluoroethylamine

Participants

Reaction Steps

At 45° C., 520 mg (2.89 mmol) of 6-chloro-3-chloromethyl-5-fluoropyridine (Va-4), 1.05 ml (14.44 mmol) of 2,2-difluoroethylamine and 400 μl (2.89 mmol) of triethylamine in 50 ml of acetonitrile are stirred for about 48 hours. During the reaction, after about 16 hours and 32 hours, a further 0.42 ml (5.78 mmol) of 2,2-difluoroethylamine are added in each case. The reaction mixture is concentrated under reduced pressure and then taken up in 1 N aqueous hydrochloric acid and washed with ethyl acetate. The aqueous phase is made alkaline using 2.5 N aqueous sodium hydroxide solution and extracted repeatedly with ethyl acetate. Drying of the combined organic phases over sodium sulphate and concentration under reduced pressure gives 370 mg (57% of theory) of N-[(6-chloro-5-fluoropyridin-3-yl)methyl]-2,2-difluoroethylamine.

Provenance & Evidence