Phosphorus oxychloride → 1-Chloro-3-methoxyisoquinoline

Participants

Reaction Steps

3-Methoxyisoquinolin-1(2H)-one (2.8 g, 16.0 mmol) in POCl3 (10 mL) was heated to reflux for 3 h then evaporated in vacuo. The residue was poured into iced NaHCO3 solution (50 mL). The product was extracted with EtOAc (2×). The organic layer was washed with brine, dried over MgSO4, filtered, evaporated. The residue was purified by flash chromatography with 20% then 40% of EtOAc/hexane to afford 1.36 g (44%) of the desired product 1-chloro-3-methoxyisoquinoline as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.29-8.16 (d, J=8.3 Hz, 1H), 7.72 (d, J=8.3 Hz, 1H), 7.63 (ddd, J=8.3, 6.8, 1.1 Hz, 1H), 7.47 (ddd, J=8.5, 7.0, 1.1 Hz, 1H), 6.98 (s, 1H), 4.05 (s, 3H). MS: MS m/z 194.0 (M++1).

Provenance & Evidence