Triphenylphosphine → HCID 12986047, compound

3-(3-Methoxymethoxypyridin-4-yl)-1-propanol (1.59 g, 9.2 mmol) obtained in Example 2 and triphenylphosphine (2.78 g, 10.6 mmol) are dissolved in THF (40 ml), and thereto are successively added with stirring diisopropyl azodicarboxylate (1.85 g, 9.2 mmol) and 2-(3-bromophenylthio)-3-pyridinol (2.00 g, 7.1 mmol) obtained in Reference Example 1 under ice-cooling. The mixture is stirred at room temperature 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 15% aqueous hydrochloric acid solution (10 ml), and the mixture is heated under reflux for 30 minutes. The reaction solution is concentrated under reduced pressure, 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: chloroform/ethyl acetate), and further recrystallized from diethyl ether to give the title compound (1.98 g) as colorless crystals, m.p. 169-171° C.

1. customobtained in Reference Example 1 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 15% aqueous hydrochloric acid solution (10 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: chloroform/ethyl acetate)
19. customfurther recrystallized from diethyl ether

ORD record

ord-1b2fb7238e784641bd1f359d5e474c2b

Source dataset

uspto-grants-2003_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06555557B1