General procedure for the synthesis of 3-(trifluoromethoxy)pyridin-4-amine from 2-chloro-3-(trifluoromethoxy)pyridin-4-amine: palladium (10% activated charcoal, 470 mg) was added to a 4-amino-2-chloro-3-trifluoromethoxypyridine (20,1.5 g, 7.0 mmol) and ammonium formate (880 mg, 14.0 mmol, 2 eq.) at 25 °C in a in a solution of methanol (12 mL) was stirred. The reaction mixture was stirred at 55 °C for 16 h, followed by filtration and evaporation of the solvent. The residue was partitioned between ethyl acetate (2 x 20 mL) and water (30 mL). The organic layers were combined, dried over sodium sulfate and evaporated. Purification of the crude yellow oil by vacuum distillation afforded 4-amino-3-trifluoromethoxypyridine as a colorless oil (21,1.0 g, 5.6 mmol, 80% yield); boiling point 110-114 °C/14 mbar.1H NMR (CDCl3, 300 MHz): δ=8.19 (s,1H), 8.05 (d,J=5.5 Hz,1H). 6.59 (d,J=5.5Hz,1H), 4.41 (bs,2H).19F NMR (CDCl3,282MHz): δ=-58.7.13C NMR (CD3OD,75MHz): δ=150.8,148.5,143.5,132.9,120.8 (q,J=259Hz),110.4. Elemental analysis (C6H5F3N2O, molecular weight 178): calculated value C 40.46%, H 2.83%, N 15.73%; measured value C 40.28%, H 2.74%, N 15.94%.
