5'-TRIFLUOROMETHYL-3,4,5,6-TETRAHYDRO-2H-[1,2']BIPYRIDINYL-4-CARBOXYLIC ACID

420844-59-3

406476-31-1

The general procedure for the synthesis of 1-[5-(trifluoromethyl)-2-pyridinyl]piperidine-4-carboxylic acid from ethyl 1-(5-(trifluoromethyl)pyridin-2-yl)piperidine-4-carboxylate was as follows: ethyl 1-[5-(trifluoromethyl)pyridin-2-yl]piperidine-4-carboxylate, in crude form, was dissolved in a solvent mixture of 15 mL methanol and 2.5 mL water. 535 mg (9.54 mmol) of potassium hydroxide was added and the reaction mixture was stirred at 40 °C for 30 min. Upon completion of the reaction, the solvent was removed by evaporation and the residue was dissolved in water and the pH was adjusted to 3 with 2 N hydrochloric acid solution. the precipitated solid was collected by filtration and dried under vacuum to afford 471 mg (54% yield) of the target product 1-[5-(trifluoromethyl)-2-pyridyl]piperidine-4-carboxylic acid. The product was characterized by 1H NMR (DMSO-d6): δ 1.42-1.60 (m, 2H), 1.81-1.93 (m, 2H), 2.50-2.62 (m, 1H), 3.00-3.14 (m, 2H), 4.21-4.36 (m, 2H), 6.95 (d, 1H), 7.75 (dd, 1H), 8.38 (d , 1H), 12.25 (s, 1H). The molecular weight was 274.24 and mass spectral analysis showed m/z = 275 (M + H)+.