Phosphorus trichloride → Chloro-6-[2-(2-methoxyethoxy)ethoxy]isoquinoline

Phosphorus trichloride (60 mL) and 6-[2-(2-methoxyethoxy)ethoxy]-2H-isoquinolin-1-one (3.38 g, 14.3 mmol) were stirred at reflux under nitrogen atmosphere for 2 h. The reaction solution was cooled to room temperature and concentrated in vacuo until 10 mL remained. The obtained oil was poured onto ice water (80 mL) and stirred for 1 h. The mixture was neutralized with addition of solid potassium carbonate and extracted with methylene chloride (3×80 mL). The combined organic layer was washed with water (50 mL) and brine (50 mL), dried over sodium sulphate, filtered and concentrated. The obtained oil was pre-absorbed on silica gel and purified by flash chromatography (gradient:hexane/ethyl acetate, 6:4→4:6). The appropriate fractions were pooled, concentrated and dried to give 1.24 g (30% yield) of the title compound as a waxy solid. MS (AP+) m/z 282 (M+1).

1. temperatureat reflux under nitrogen atmosphere for 2 h
2. concentrationconcentrated in vacuo until 10 mL
3. additionThe obtained oil was poured onto ice water (80 mL)
4. additionThe mixture was neutralized with addition of solid potassium carbonate
5. extractionextracted with methylene chloride (3×80 mL)
6. washThe combined organic layer was washed with water (50 mL) and brine (50 mL)
7. dry with materialdried over sodium sulphate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe obtained oil was pre-absorbed on silica gel
11. custompurified by flash chromatography (gradient:hexane/ethyl acetate, 6:4→4:6)
12. concentrationconcentrated
13. customdried

ORD record

ord-8d1eb2b8f6ed42f596467ba546835b71

Source dataset

uspto-grants-2007_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07205314B2