Phosphorus oxychloride → 1-Chloro-6-methoxyisoquinoline

Temperature

110 °C

A suspension of 6-Methoxy-2H-isoquinolin-1-one (900 mgs, 5.1 mmol) in POCl3 (4 mL) was heated at 110° C. for 3 h (clear solution obtained upon heating). After 3 h, the reaction mixture was concentrated under reduced pressure. The residue was poured into iced water (10 mL), pH was then adjusted to 10 with 3N NaOH and extracted with CHCl3 (3×25 mL). The combined CHCl3 layers were washed with brine and dried (MgSO4). The organic layer was then filtered, concentrated and purified by flash chromatography (50% ethyl acetate/hexane) to give 1-chloro-6-methoxy-isoquinoline (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), pH
4. extractionextracted with CHCl3 (3×25 mL)
5. washThe combined CHCl3 layers were washed with brine
6. dry with materialdried (MgSO4)
7. filtrationThe organic layer was then filtered
8. concentrationconcentrated
9. custompurified by flash chromatography (50% ethyl acetate/hexane)

ORD record

ord-fd5f16b6d3a24196a05bac8c0ab253d9

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08518874B2