反应详情

温度

130 °C

Powdered potassium hydroxide (55 mg, 0.98 mmol) followed by 4-chloro-6,7-dimethoxyquinoline (200 mg, 0.89 mmol), (prepared as described for the starting material in Example 2), was added to 2-fluoro-5-hydroxy-4-methylphenol (600 mg, 4.2 mmol) heated at 130° C. and the mixture then stirred for 1.5 hours at 145° C. The mixture was allowed to cool then partitioned between ethyl acetate and water and the aqueous layer was adjusted to pH7 with 5M hydrochloric acid. The organic layer was separated, washed with brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by preparative reverse-phase HPLC eluting with water/methanol (90/10 to 30/o) to give 6,7-dimethoxy-4-(2-fluoro-5-hydroxy-4-methylphenoxy)quinoline (65 mg, 22%) as a white solid.

1. custom(prepared
2. temperatureto cool
3. customthen partitioned between ethyl acetate and water
4. customThe organic layer was separated
5. washwashed with brine
6. dry with materialdried (MgSO4)
7. customthe solvent removed by evaporation
8. customThe residue was purified by preparative reverse-phase
9. washHPLC eluting with water/methanol (90/10 to 30/o)