Acetic Anhydride → (4-((2-Methoxy-1,3-dioxan-5-yl)methoxy)-3-methylpyridin-2-yl)methanol

Temperature

100 °C

The 4-((2-methoxy-1,3-dioxan-5-yl)methoxy)-2,3-dimethylpyridine 1-oxide (1.8 g, 6.68 ml) obtained in the step (6b) was mixed with acetic anhydride (8 ml). The mixture was stirred at 100° C. for 2 hours. After cooled to room temperature, the reaction mixture was concentrated under reduced pressure. To the residue, methanol (10 ml) and a 5N aqueous sodium hydroxide solution (5 ml) were added and the mixture was stirred at room temperature for 15 hours. The reaction mixture was concentrated and the residue was separated with a saturated saline solution and ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, concentrated and the residue was purified by silica gel column chromatography (elution solvent: heptane/ethyl acetate, ethyl acetate/methanol) to obtain the title compound (0.41 g, yield: 22.8%), which is a cis and trans (1:1) mixture, as a yellow oil.

1. temperatureAfter cooled to room temperature
2. concentrationthe reaction mixture was concentrated under reduced pressure
3. additionTo the residue, methanol (10 ml) and a 5N aqueous sodium hydroxide solution (5 ml) were added
4. stirringthe mixture was stirred at room temperature for 15 hours
5. concentrationThe reaction mixture was concentrated
6. customthe residue was separated with a saturated saline solution and ethyl acetate
7. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customthe residue was purified by silica gel column chromatography (elution solvent: heptane/ethyl acetate, ethyl acetate/methanol)

ORD record

ord-765c5ab30ba54739a7d77480c20b5ee4

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08124780B2