280566-45-2

124-38-9

39890-95-4

280566-45-2

Lithium diisopropylammonium (LDA) (44.2 g, 1.5 eq.) was added slowly and dropwise to a stirred tetrahydrofuran (1.0 L) solution of 2-chloro-6-(trifluoromethyl)pyridine (50.0 g, 1.0 eq.) at -78 °C. The reaction temperature was maintained at -78°C and after 2 hours of reaction, carbon dioxide (500 g) was passed into the reaction mixture. The reaction mixture was gradually warmed to room temperature and stirring was continued for 10 minutes. The reaction progress was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the reaction mixture was acidified to pH 2 with 1N hydrochloric acid and then extracted with ethyl acetate (2 x 500 mL). The organic layers were combined, washed sequentially with water (500 mL) and brine (500 mL), dried with anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was co-milled with petroleum ether to obtain pure 2-chloro-6-(trifluoromethyl)nicotinic acid (Int-15) (40.0 g, yield 64.6%).