4.1.9 Synthesis of 6-bromo-4-iodoquinoline (12): To an anhydrous ethyl acetate (20 mL) solution of 6-bromo-4-chloroquinoline (11) (3.50 g, 14.46 mmol) was added hydrochloric acid saturated ethyl acetate (40 mL), and the formation of a white precipitate was immediately observed. After stirring for 30 min, the suspension was concentrated under vacuum to give 6-bromo-4-chloroquinoline hydrochloride as an off-white solid (3.91 g, 14.14 mmol). Subsequently, 6-bromo-4-chloroquinoline hydrochloride (3.91 g, 14.14 mmol), anhydrous potassium iodide (9.76 g, 70.70 mmol), and anhydrous acetonitrile (100 mL) were added in a two-neck flask. The resulting slurry was stirred under reflux conditions for 48 hours and then cooled to room temperature. The reaction mixture was treated with saturated aqueous sodium bicarbonate solution (40 mL) and 5% sodium sulfite solution (20 mL). The reaction mixture was extracted with dichloromethane (200 mL x 2), and the combined organic phases were dried over magnesium sulfate and concentrated under vacuum to give the crude product. The crude product was further purified by silica gel column chromatography (25% ethyl acetate/petroleum ether) to afford the target compound 6-bromo-4-iodoquinoline (4.42 g, 13.27 mmol, 94% yield) as an off-white solid. 1H NMR (500 MHz, DMSO-d6) δ 8.51 (d, J = 4.5 Hz, 1H, Ar-H), 8.21 (d, J = 4.5 Hz, 1H, Ar-H), 8.11 (t, J = 1.5 Hz, 1H, Ar-H), 7.97-7.91 (m, 2H, Ar-H). ESI-MS: m/z = 334 [M + H]+.
