131747-42-7

124-38-9

189278-27-1

131747-42-7

General procedure for the synthesis of 6-(trifluoromethyl)pyridine-2-carboxylic acid from carbon dioxide and 2-bromo-6-trifluoromethylpyridine: 1. 2-Bromo-6-(trifluoromethyl)pyridine (100 mg, 0.44 mmol, 1 eq.) was dissolved in anhydrous ether at room temperature and protected by nitrogen and subsequently cooled to -70 °C. 2. 1.6 M hexane solution of n-butyllithium (0.28 mL, 0.44 mmol, 1 eq.) was added slowly and dropwise through the addition funnel. 3. The reaction mixture was stirred at -40 °C for 15 minutes and then cooled to -70 °C again. 4. Carbon dioxide gas was introduced into the reaction mixture and continuously bubbled for 10 minutes. 5. Allow the reaction mixture to warm slowly to room temperature. 6. 6. the reaction was terminated by addition of water and subsequently washed three times with ether. 7. Adjust the pH of the aqueous layer to 3 with concentrated hydrochloric acid. 8. Extracted the acidic aqueous layer with ethyl acetate three times. 9. The ethyl acetate layers were combined, dried with anhydrous sodium sulfate and concentrated under reduced pressure to give 6-(trifluoromethyl)pyridine-2-carboxylic acid (30 mg) as a white solid in 35% yield. 10. The product was detected by LCMS and the molecular ion peak (M + H)+ = 192.06 was confirmed.