Phosphorus oxychloride → 1-Chloro-6-methoxyisoquinoline

Participants

Reaction Conditions

Reaction Steps

A suspension of 6-methoxyisoquinolin-1(2H)-one (900 mgs, 5.1 mmol) in phosphorus oxychloride (POCl3, 4 mL) was heated at 110° C. for 3 hours (clear solution obtained upon heating). After 3 hours, the reaction mixture was concentrated under reduced pressure. The residue was poured into iced water (10 mL), the pH was then adjusted to 10 with 3N sodium hydroxide, and the mixture extracted with chloroform (3×25 mL). The combined chloroform layers were washed with brine and dried over magnesium sulfate. The organic layer was then filtered, concentrated under reduced pressure, and purified by flash chromatography (50% ethyl acetate/hexane) to give 1-chloro-6-methoxyisoquinoline (720 mgs, 3.7 mmol, 73% yield) as white solid. 1H NMR (CD3OD): 8.23 (d, 1H, J=8.8 Hz); 8.11 (d, 1H, J=6.0 Hz); 7.69 (d, 1H, J=6.0 Hz); 7.37-7.33 (m, 2H); 3.97 (s, 3H). MS m/z 194 (M++H).

Provenance & Evidence