Example 1 Synthesis of 2-chloro-5-methoxyquinoline: 5-methoxyquinoline (104.3 mg, 0.655 mmol) was dissolved in dichloromethane (3 mL), and m-chloroperoxybenzoic acid (mCPBA; 195 mg, 1.13 mmol) was slowly added at 0 °C. The reaction mixture was stirred at 0 °C for 30 min and then gradually warmed up to room temperature and continued stirring for 3 h. The reaction was carried out by thin layer chromatography (TLC). The reaction process was monitored by thin layer chromatography (TLC, unfolding agent ratio: ethyl acetate/dichloromethane/hexane = 1:2:4). After completion of the reaction, the organic layer was separated by extraction with 4N NaOH aqueous solution and dichloromethane. The organic layer was dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure to give a white solid. The solid was dissolved in dichloromethane (2.5 mL), phosphorus oxychloride (POCl3; 0.09 mL, 0.992 mmol) was added, and the mixture was refluxed for 3 hours at 60 °C. The reaction progression was monitored by TLC (unfolding agent ratio: ethyl acetate/chloroform/hexane = 1:2:10). Upon completion of the reaction, the reaction was cooled to room temperature and the pH was adjusted to 10 by slow addition of ice-water mixture followed by dropwise addition of 4N NaOH aqueous solution.The reaction mixture was extracted with distilled water and dichloromethane and the organic layer was separated. The organic layer was dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure and purified by column chromatography (eluent ratio: ethyl acetate/chloroform/n-hexane=1:2:10, Rf=0.6) to afford 2-chloro-5-methoxyquinoline (40.1 mg, yield 32%) as a white solid.1H NMR (CDCl3, 300 MHz) δ 4.01 (s, 3H) 6.88 (dd, J=7.2, 1.5 Hz, 1H), 7.35 (d, J=8.7 Hz, 1H), 7.59-7.67 (m, 2H), 8.51 (d, J=8.7 Hz, 1H).
