反应详情

温度

85 °C

The 4-(5,7-dioxaspiro[2.5]oct-6-ylmethoxy)-2,3-dimethylpyridine 1-oxide (1.8 g, 6.78 mmol) obtained by the step (2c) was mixed with acetic anhydride (5.77 ml, 61 mmol). The mixture was stirred at 85° C. for 45 minutes and then acetic anhydride was distilled off. The residue was cooled on ice and dissolved in methanol. To this, a 5N aqueous sodium hydroxide solution (2.98 ml, 14.9 mmol) was added under ice-cool and the mixture was stirred at room temperature for 2 hours. Methanol was distilled off and water was added to the residue, which was then extracted with ethyl acetate. The organic layer was washed with a saturated saline solution and dried over anhydrous magnesium sulfate, and thereafter the solvent was distilled off. Purification was performed by silica gel column chromatography (silica gel: 100 g, elution solvent: ethyl acetate/heptane=1/4 to 4/1). To the purified product, heptane (15 ml) was added and the mixture was refluxed. After the solution was confirmed to reach a homogeneous state, it was gradually cooled. The precipitated product was obtained by filtration. In this manner, the title compound (520 mg, yield: 28.9%) was obtained as a white solid.

1. distillationacetic anhydride was distilled off
2. temperatureThe residue was cooled on ice
3. dissolutiondissolved in methanol
4. temperaturecool
5. stirringthe mixture was stirred at room temperature for 2 hours
6. distillationMethanol was distilled off
7. additionwater was added to the residue, which
8. extractionwas then extracted with ethyl acetate
9. washThe organic layer was washed with a saturated saline solution
10. dry with materialdried over anhydrous magnesium sulfate
11. distillationthe solvent was distilled off
12. customPurification
13. washwas performed by silica gel column chromatography (silica gel: 100 g, elution solvent: ethyl acetate/heptane=1/4 to 4/1)
14. additionTo the purified product, heptane (15 ml) was added
15. temperaturethe mixture was refluxed
16. temperaturewas gradually cooled
17. customThe precipitated product was obtained by filtration