General procedure for the synthesis of 4-fluoroisoquinoline from 4-bromoisoquinoline: A solution of 4-bromoisoquinoline (20 g, 96.6 mmol) dissolved in 144 mL of THF was added slowly and dropwise to a 760 mL THF solution containing n-butyllithium (133 mL, 332.5 mmol, 2.5 M in THF) at -65 °C. After the dropwise addition was completed, the reaction mixture was continued to be stirred at -65 °C for 30 min. Subsequently, a solution of N-fluorobenzenesulfonimide (66.68 g, 211.7 mmol) dissolved in 216 mL THF was added dropwise at the same temperature. After addition, the reaction was maintained at -65 °C for 1 hour. Upon completion of the reaction, the mixture was slowly warmed to room temperature and the reaction was quenched by the addition of 300 mL of saturated aqueous ammonium chloride. The reaction mixture was extracted with ethyl acetate (300 mL x 3), and the combined organic phases were washed with 300 mL of saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (elution gradient: 0-100% ethyl acetate/petroleum ether) to afford 4-fluoroisoquinoline (8.5 g, red oil, yield: 60%).
