Phosphorus oxychloride → 1-Chloro-6-methoxyisoquinoline

Temperature

110 °C

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).

1. custom(clear solution obtained upon heating)
2. concentrationthe reaction mixture was concentrated under reduced pressure
3. additionThe residue was poured into iced water (10 mL)
4. extractionthe mixture extracted with chloroform (3×25 mL)
5. washThe combined chloroform layers were washed with brine
6. dry with materialdried over magnesium sulfate
7. filtrationThe organic layer was then filtered
8. concentrationconcentrated under reduced pressure
9. custompurified by flash chromatography (50% ethyl acetate/hexane)

ORD record

ord-67dae8a1ec1a43ba9b6d53bdd95b6b4e

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08211897B2