[Synthesis]
General procedure for the synthesis of 2-(trifluoromethoxy)pyridine-3-carboxylic acid from 6-chloro-2-(trifluoromethoxy)nicotinic acid: palladium catalyst (10% loaded on charcoal, 450 mg) was added to a solution of 6-chloro-2-(trifluoromethoxy)nicotinic acid (37,1.5 g, 6.2 mmol) and ammonium formate (790 mg, 12.4 mmol, 2.0 equivalent) in a solution of methanol (10 mL). The reaction mixture was stirred at 55 °C for 16 hours. Upon completion of the reaction, the catalyst was removed by filtration and the filtrate was concentrated by rotary evaporation. The residue was extracted by partitioning between ethyl acetate (2 x 20 mL) and 2.0 M hydrochloric acid (30 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and the solvent evaporated to give pure 2-(trifluoromethoxy)pyridine-3-carboxylic acid (38,1.05 g, 5.0 mmol, 81% yield) as a white powder with a melting point of 82-85 °C. The product was structurally confirmed by 1H NMR (CD3OD, 300 MHz), 19F NMR ((CD3)2CO, 282 MHz) and 13C NMR (CD3OD, 75 MHz), and elemental analysis was performed (C7H4F3NO3, calculated value: C 40.59%, H 1.95%, N 6.76%; measured value: C 40.35%, H 2.03%, N 6.65%) to verify the purity. |