3-Bromo-5-fluoro-4-pyridinecarboxylic acid

124-38-9

955372-86-8

General procedure for the synthesis of 3-bromo-5-fluoroisonicotinic acid from carbon dioxide: Intermediate 6: 3-bromo-5-fluoroisonicotinic acid; n-butyllithium (12.5 mL, 2.5 M solution of THF, 31.3 mmol) was slowly added to a solution of diisopropylamine (4.4 mL, 31.3 mmol) in THF (200 mL) at 0 °C and stirred for 15 min, then cooled to -78 °C. 3-Bromo-5-fluoropyridine (5.0 g, 28.4 mmol) solid was added and the resulting solution was stirred at -78 °C for 10 min. A gaseous carbon dioxide bulb was passed through a cannula into the solution for 30 min and the resulting solution was stirred for 2 h. The solution was warmed from -78 °C to room temperature. The reaction solution was concentrated by rotary evaporation, diluted with 2 M NaOH and washed with EtOAc. The aqueous solution was acidified with 1M HCl and extracted with EtOAc. The organic extract was washed with brine, dried over MgSO4, filtered and concentrated to give the target product 3-bromo-5-fluoroisonicotinic acid (4.75 g, 76% yield) as a solid.