反应详情

A mixture of 4-chloro-6-methoxy-7-(2-([1,2,4]-triazol-1-yl)ethoxy)quinoline (132 mg, 0.43 mmol), 4-chloro-2-fluorophenol (400 mg, 2.7 mmol) and potassium hydroxide (28 mg, 0.49 mmol) was head at 165° C. for 3 hours under argon. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with water, brine, dried (MgSO4) and the volatiles were removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5). The purified product was dissolved in methylene chloride and 2M ethereal hydrogen chloride (0.5 ml) was added. The volatiles were removed by evaporation and the residue was triturated with ether, collected by filtration and dried under vacuum to give 4-(4-chloro-2-fluorophenoxy)-6-methoxy-7-(2-([1,2,4]-triazol-1-yl)ethoxy)quinoline hydrochloride (110 mg, 61%).

1. customat 165° C.
2. customfor 3 hours
3. customThe mixture was partitioned between ethyl acetate and water
4. washThe organic layer was washed with water, brine
5. dry with materialdried (MgSO4)
6. customthe volatiles were removed by evaporation
7. customThe residue was purified by column chromatography
8. washeluting with methylene chloride/methanol (95/5)
9. dissolutionThe purified product was dissolved in methylene chloride
10. addition2M ethereal hydrogen chloride (0.5 ml) was added
11. customThe volatiles were removed by evaporation
12. customthe residue was triturated with ether
13. filtrationcollected by filtration
14. customdried under vacuum