反应详情

Sodium hydride (60% in mineral oil, 0.08 g, 2.0 mmol) is suspended in DMF (5 ml), and thereto is added 2-phenoxy-3-[3-(3-hydroxypyridin-4-yl)propoxy]pyridine (0.20 g, 0.62 mmol) obtained in Example 30 at room temperature, and the mixture is stirred for 30 minutes. To the mixture is added 2-methoxymethoxyethyl bromide (0.32 g, 2.0 mmol) under ice-cooling, and the mixture is stirred at 50° C. for 30 minutes. To the reaction solution is added chloroform (100 ml), and the mixture is washed with a saturated brine (50 ml×2), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. To the residue are added ethanol (20 ml) and a 35% aqueous hydrochloric acid solution (2 ml), and the mixture is stirred at 60° C. for 30 minutes. The pH value of the reaction solution is adjusted to pH 10 with a saturated aqueous sodium hydrogen carbonate solution, and the mixture is extracted with chloroform (50 ml×2), washed with a saturated brine (50 ml×2), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (eluent: chloroform/methanol) to give 2-phenoxy-3-[3-(3-(2-hydroxyethoxy)pyridin-4-yl)propoxy]pyridine, which is further treated with fumaric acid to give the title compound (0.17 g), m.p. 129-132° C. (recrystallized from ethanol/isopropyl ether).

1. temperaturecooling
2. stirringthe mixture is stirred at 50° C. for 30 minutes
3. washthe mixture is washed with a saturated brine (50 ml×2)
4. dry with materialdried over anhydrous magnesium sulfate
5. concentrationconcentrated under reduced pressure
6. additionTo the residue are added ethanol (20 ml)
7. stirringa 35% aqueous hydrochloric acid solution (2 ml), and the mixture is stirred at 60° C. for 30 minutes
8. extractionthe mixture is extracted with chloroform (50 ml×2)
9. washwashed with a saturated brine (50 ml×2)
10. dry with materialdried over anhydrous magnesium sulfate
11. concentrationconcentrated under reduced pressure
12. customThe residue is purified by silica gel column chromatography (eluent: chloroform/methanol)