反应详情

4-Chloro-2-fluoro-5-hydroxyaniline (194 mg, 1.2 mmol), (as described in EP 61741 A2), was added to a suspension of 4-chloro-6,7-dimethoxy-3-fluoroquinoline (241 mg, 1 mmol) in 2-pentanol (5 ml). After refluxing for 15 hours, the precipitate was collected by filtration, washed with isopropanol and dried under vacuum. The solid was partitioned between ethyl acetate and aqueous sodium hydrogen carbonate. 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/isopropanol and 5M hydrogen chloride in isopropanol (0.5 ml) was added. After evaporation of the methylene chloride, the precipitate was collected by filtration, washed with isopropanol, followed by ether and dried under vacuum to give 6,7-dimethoxy-3-fluoro-4-(4-chloro-2-fluoro-hydroxyanilino)quinoline hydrochloride (150 mg, 37%).

1. temperatureAfter refluxing for 15 hours
2. filtrationthe precipitate was collected by filtration
3. washwashed with isopropanol
4. customdried under vacuum
5. customThe solid was partitioned between ethyl acetate and aqueous sodium hydrogen carbonate
6. washThe organic layer was washed with water, brine
7. dry with materialdried (MgSO4)
8. customthe volatiles were removed by evaporation
9. customThe residue was purified by column chromatography
10. washeluting with methylene chloride/methanol 95/5
11. dissolutionThe purified product was dissolved in methylene chloride/isopropanol
12. addition5M hydrogen chloride in isopropanol (0.5 ml) was added
13. customAfter evaporation of the methylene chloride
14. filtrationthe precipitate was collected by filtration
15. washwashed with isopropanol
16. customdried under vacuum