General procedure for the synthesis of 4-chloro-7-fluoroquinoline from 7-fluoro-4-hydroxyquinoline: 7-fluoro-4-hydroxyquinoline (1.1 g, 6.7 mmol) was added to an oven-dried round-bottomed flask, followed by the addition of pure phosphorus oxychloride (15 mL). The reaction mixture was heated and stirred at 70 °C for 3 hours. Upon completion of the reaction, the reaction solution was concentrated under reduced pressure, and then the concentrate was carefully poured into pre-cooled ice water (30 mL) and neutralized to pH neutral with aqueous sodium bicarbonate. The aqueous phase was extracted several times with dichloromethane (5 × 20 mL), and the combined organic phases were washed with saturated saline, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to remove the solvent. The crude product was purified by silica gel column chromatography with the eluent being a hexane solution of 10%-40% ethyl acetate to afford the target product 4-chloro-7-fluoroquinoline (1.2 g, 98% yield) as a white solid. the Rf value was 0.7 (hexane solution of 40% ethyl acetate, UV activity). Mass Spectrometry (ESI) m/z (M+H) calculated value: 182.59, measured value: 182.6. 1H-NMR (500 MHz, CDCl3) δ 8.71 (d, J = 3.6 Hz, 1H), 8.32-8.21 (m, 1H), 7.69-7.64 (m, 1H), 7.59 (d, J = 3.6 Hz, 1H). 7.52-7.41 (m, 1H).13C-NMR (100 MHz, CDCl3) δ 164.7, 162.2, 151.03, 150.24, 150.11, 142.66, 126.58, 126.49, 123.54, 120.61, 118.19, 177.94, 113.56, 113.35.
