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

Temperature

100 °C

The 4-((2,2-bis(fluoromethyl)-1,3-dioxan-5-yl)methoxy)-2,3-dimethylpyridine 1-oxide (1.63 g, 5.37 mmol) obtained in the step (7b) was mixed with acetic anhydride (8 ml). The mixture was stirred at 100° C. for 2 hours, cooled to room temperature, and then, 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 3 hours. The reaction mixture was concentrated and the residue was separated between 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 (385 mg, yield 23.6%) as a yellow oil.

1. temperaturecooled to room temperature
2. concentrationconcentrated 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 3 hours
5. concentrationThe reaction mixture was concentrated
6. customthe residue was separated between 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-b2e02dfa9d164c7ab9096a136bf8f1a3

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08124780B2