Synthesis
General procedure for the synthesis of 8-chloroisoquinoline from 5-bromo-8-chloroisoquinoline: 5-bromo-8-chloroisoquinoline (1.20 g, 4.95 mmol, 1.0 eq.), 2-methyltetrahydrofuran (10 mL), and methanol (10 mL) were added to a single-necked glass flask, and then passed through nitrogen for degassing. Under an inert atmosphere, 10% palladium/carbon catalyst (530 mg, 0.5 mmol, 0.1 eq.) was added, followed by slow addition of sodium borohydride (206 mg, 5.45 mmol, 1.1 eq.). The flask was sealed with a gas bubbler filled with silicone oil. The mixture was stirred at 25 °C for 70 min (prolonged reaction time leads to the formation of excess by-products such as 1,2,3,4-tetrahydro-diisoquinoline and 8-chloro-1,2,3,4-tetrahydroisoquinoline) before the reaction was quenched with glacial acetic acid (500 μL, 8.74 mmol, 1.75 equiv). After continued stirring for 10 min, the reaction mixture was filtered through diatomaceous earth. The filter cake was washed with methanol and dichloromethane. The filtrate was concentrated and the residue was purified by fast column chromatography (silica gel, hexane-ethyl acetate, 93:7) to give an off-white crystalline product. Yield: 360 mg (44%); melting point 50-55 °C. IR (ATR): 1620, 1553, 1429, 1379, 1300, 1204, 1038, 970, 827, 748, 686, 634, 534 cm^-1. 1H NMR (400 MHz, CDCl3): δ = 9.66 (s, 1H). 8.60 (d, J=5.7Hz, 1H), 7.73 (d, J=7.9Hz, 1H), 7.69-7.56 (m, 3H).13C NMR (100MHz, CDCl3): δ=149.4, 143.8, 137.1, 132.5, 130.3, 127.5, 125.6, 125.7, 120.1 .
