Step 1: Preparation of 1-chloro-4-methoxyisoquinoline
To a solution of 1-chloro-4-hydroxyisoquinoline (5.0 g, 27.8 mmol) in acetonitrile (50 mL) was slowly added trimethylsilylated diazomethane (12.73 g, 111.2 mmol). The reaction mixture was stirred at 0 °C, gradually warmed to room temperature and continued stirring for 2 hours. After completion of the reaction, the solvent was removed by distillation under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography to afford 1-chloro-4-methoxyisoquinoline (2.5 g, 46.4% yield) as an off-white solid. The structure of the product was confirmed by 1H NMR (400 MHz, CD3OD) and mass spectrometry: 1H NMR δ 8.29-8.17 (m, 2H), 7.97 (s, 1H), 7.91-7.82 (m, 2H), 4.05 (s, 3H); MS m/z 194.7 (M++1).
