2-CHLORO-4-IODO-6-(TRIFLUOROMETHYL)PYRIDINE

205240-59-1

205444-22-0

The general procedure for the synthesis of 2-chloro-4-iodo-6-(trifluoromethyl)pyridine from 2-chloro-3-iodo-6-(trifluoromethyl)pyridine was carried out as follows: 2-chloro-3-iodo-6-(trifluoromethyl)pyridine (3.07 g, 10.0 mmol) was dissolved in tetrahydrofuran (35 mL) under nitrogen protection and cooled to -78 °C. Subsequently, a solution of lithium diisopropylammonium (LDA, 5.5 mL, 2 M) was added slowly dropwise via syringe. The reaction mixture was stirred at -78 °C for 1 hour. Upon completion of the reaction, the reaction was quenched with 1 M aqueous hydrochloric acid solution (15 mL) at -78 °C and stirring was continued for 0.5 hr. The reaction mixture was gradually warmed to room temperature and stirred for another 0.5 hr. Subsequently, the mixture was concentrated under reduced pressure to remove the solvent. The aqueous layer was separated and extracted with ethyl acetate (2 x 100 mL). The organic layers were combined, washed sequentially with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (using petroleum ether as eluent) to afford the target product 2-chloro-4-iodo-6-(trifluoromethyl)pyridine (2.5 g, 81% yield) as a white solid. Its NMR hydrogen spectrum (400 MHz, DMSO-d6) data were as follows: δ 8.39 (s, 1H), 8.34 (s, 1H).