Synthesis
General procedure for the synthesis of 2-chloro-3-fluoro-5-nitropyridine from 3-fluoro-5-nitropyridin-2(1H)-one: To a stirred solution of 3-fluoro-5-nitropyridin-2-ol (1.5 g, 9.48 mmol) in phosphorus trichloride (15 mL) was slowly added phosphorus pentachloride (2.96 g, 14.22 mmol) at 60 °C. The reaction mixture was kept continuously stirred at 60 °C for 10 hours. After the reaction was completed, the mixture was cooled to room temperature and carefully poured into crushed ice. Extraction was carried out with ethyl acetate (3 x 20 mL). The organic layers were combined and washed with saturated sodium carbonate solution (25 mL) and subsequently dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure to give the crude product. Finally, the crude product was purified by silica gel column chromatography (100-200 mesh, eluent 5% ethyl acetate in hexane solution) to afford the target compound 2-chloro-3-fluoro-5-nitropyridine (1.62 g, 97% yield).
References
[1] Patent: WO2013/13817, 2013, A1. Location in patent: Page/Page column 96; 97
[2] Patent: WO2013/13815, 2013, A1. Location in patent: Page/Page column 131
[3] Patent: US2013/29961, 2013, A1. Location in patent: Paragraph 0656
[4] Patent: US2013/29962, 2013, A1. Location in patent: Paragraph 0761
[5] MedChemComm, 2016, vol. 7, # 5, p. 1022 - 1032
