2-Methoxyethanol → 2-Phenoxy-3-[3-(3-methoxyethoxypyridin-4-yl)propoxy]pyridine

Temperature

60 °C

2-Methoxyethanol (0.08 g, 0.93 mmol) and triphenylphosphine (0.32 g, 1.2 mmol) are dissolved in THF (20 ml), and thereto are successively added with stirring diisopropyl azodicarboxylate (0.17 g, 0.93 mmol) and 2-phenoxy-3-[3-(3-hydroxypyridin-4-yl)propoxy]pyridine (0.20 g, 0.62 mmol) obtained in Example 30 under ice-cooling. The mixture is further stirred at 60° C. for one hour, 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 (50 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: ethyl acetate/methanol) to give 2-phenoxy-3-[3-(3-methoxyethoxypyridin-4-yl)propoxy]pyridine, which is further treated with fumaric acid to give the title compound (0.12 g), m.p. 120-123° C. (recrystallized from diethyl ether).

1. temperaturecooling
2. concentrationthe reaction solution is concentrated under reduced pressure
3. additionTo the residue is added ethyl acetate (50 ml)
4. extractionthe mixture is extracted with a 10% aqueous hydrochloric acid solution (50 ml×2)
5. extractionthe mixture is extracted with ethyl acetate (50 ml×2)
6. washThe organic layer is washed with a saturated brine (50 ml×2)
7. dry with materialdried over anhydrous magnesium sulfate
8. concentrationconcentrated under reduced pressure
9. customThe residue is purified by silica gel column chromatography (eluent: ethyl acetate/methanol)

ORD record

ord-7c29738fac3f42de8d2640025ba1c497

Source dataset

uspto-grants-2004_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06765095B2