反应详情

温度

40 °C

3-(3-Methoxymethoxypyridin-4-yl)-1-propanol (2.50 g, 12.7 mmol) obtained in Example 2 and triphenylphosphine (4.50 g, 17.0 mmol) are dissolved in THP (40 ml), and thereto are successively added with stirring diisopropyl azodicarboxylate (3.00 g, 15.0 mmol) and 2-(3-bromophenoxy)-3-pyridinol (2.50 g, 9.4 mmol) obtained in Reference Example 11 under ice-cooling. The mixture is further stirred at 40° C. for 30 minutes, and the reaction solution is concentrated under reduced pressure. To the residue is added ethyl acetate (50 ml), and the mixture is extracted with a 10% aqueous hydrochloric acid solution (50 ml×2). The pH value of the aqueous layer is adjusted to pH 12 with potassium carbonate, and the mixture is extracted with ethyl acetate (100 ml×2). The organic layer 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 (200 ml) and a 47% aqueous hydrobromic acid solution (20 ml), and the mixture is heated under reflux for 30 minutes. The reaction solution is concentrated under reduced pressure, and neutralized with a saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate (100 ml×2). The organic layer is 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: hexane/ethyl acetate/ethanol), recrystallized from ethanol/diethyl ether to give the title compound (3.10 g) as colorless crystals, m.p. 116-118° C.

1. customobtained in Reference Example 11 under ice-
2. temperaturecooling
3. concentrationthe reaction solution is concentrated under reduced pressure
4. additionTo the residue is added ethyl acetate (50 ml)
5. extractionthe mixture is extracted with a 10% aqueous hydrochloric acid solution (50 ml×2)
6. extractionthe mixture is extracted with ethyl acetate (100 ml×2)
7. washThe organic layer is washed with a saturated brine (50 ml×2)
8. dry with materialdried over anhydrous magnesium sulfate
9. concentrationconcentrated under reduced pressure
10. additionTo the residue are added ethanol (200 ml)
11. temperaturea 47% aqueous hydrobromic acid solution (20 ml), and the mixture is heated
12. temperatureunder reflux for 30 minutes
13. concentrationThe reaction solution is concentrated under reduced pressure
14. extractionextracted with ethyl acetate (100 ml×2)
15. washThe organic layer is washed with a saturated brine (50 ml×2)
16. dry with materialdried over anhydrous magnesium sulfate
17. concentrationconcentrated under reduced pressure
18. customThe residue is purified by silica gel column chromatography (eluent: hexane/ethyl acetate/ethanol)
19. customrecrystallized from ethanol/diethyl ether