反应详情

A solution of [4-difluoromethoxy-2-ethyl-8-fluoro-3-(4-oxazol-2-ylbenzyl)quinolin-5-yloxy]acetic acid methyl ester (0.73 g) in methanol (6.0 mL) and water (0.6 mL) was treated with 5.0 M aqueous lithium hydroxide solution (0.30 mL), and the resulting mixture was stirred at room temperature for 2 hours. The mixture was acidified by the addition of glacial acetic acid, concentrated under reduced pressure, and the residue partitioned between ethyl acetate and water. The organic phase was dried over magnesium sulfate, concentrated under reduced pressure, and then diluted with acetonitrile. The resulting precipitate was removed by filtration, washed with acetonitrile, and the filtrate concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a mixture of dichloromethane, methanol and glacial acetic acid (50:1:1 to 10:1:1 by volume). Further purification by preparative reverse-phase HPLC, and then column chromatography on silica gel, eluting with a mixture of dichloromethane, methanol and glacial acetic acid (40:1:0.1 to 20:1:0.1 by volume) gave title compound as a white solid (0.082 g).

1. concentrationconcentrated under reduced pressure
2. customthe residue partitioned between ethyl acetate and water
3. dry with materialThe organic phase was dried over magnesium sulfate
4. concentrationconcentrated under reduced pressure
5. additiondiluted with acetonitrile
6. customThe resulting precipitate was removed by filtration
7. washwashed with acetonitrile
8. concentrationthe filtrate concentrated under reduced pressure
9. customThe residue was purified by column chromatography on silica gel
10. washeluting with a mixture of dichloromethane, methanol and glacial acetic acid (50:1:1 to 10:1:1 by volume)
11. customFurther purification by preparative reverse-phase HPLC
12. washcolumn chromatography on silica gel, eluting with a mixture of dichloromethane, methanol and glacial acetic acid (40:1:0.1 to 20:1:0.1 by volume)