Acetic Anhydride → (3-Methyl-4-((8-methyl-1,4,7,9-tetraoxaspiro[4.5]dec-8-yl)methoxy)pyridin-2-yl)methanol

Temperatur

50 °C

The 2,3-dimethyl-4-((8-methyl-1,4,7,9-tetraoxaspiro[4.5]dec-8-yl)methoxy)pyridine 1-oxide (1.20 g, 3.84 mmol) obtained in the step (5d) was mixed with acetic anhydride (10 ml). To the mixture, triethylamine (0.8 ml, 5.74 mmol) was added and the mixture was stirred at 50° C. for 2 hours. The reaction mixture was concentrated and methanol (10 ml) was added to the residue. Thereafter a 5N aqueous sodium hydroxide solution (7 ml) was added to the mixture, and stirred at room temperature for 30 minutes. To the resultant mixture, a saturated aqueous ammonium chloride solution (7 ml) was added and the pH was adjusted to about 10. The reaction mixture was diluted with ethyl acetate, and the organic layer was washed with a 2N aqueous sodium hydroxide solution, water, and a saline solution, dried over anhydrous sodium sulfate and concentrated. The obtained crude product was purified by silica gel column chromatography (elution solvent: ethyl acetate/methanol=1/0-4/1 gradient) and a desired fraction(s) was concentrated to obtain the title compound (312 mg, 26.1% yield) as a light yellow solid.

1. concentrationThe reaction mixture was concentrated
2. additionmethanol (10 ml) was added to the residue
3. additionThereafter a 5N aqueous sodium hydroxide solution (7 ml) was added to the mixture
4. stirringstirred at room temperature for 30 minutes
5. additionTo the resultant mixture, a saturated aqueous ammonium chloride solution (7 ml) was added
6. additionThe reaction mixture was diluted with ethyl acetate
7. washthe organic layer was washed with a 2N aqueous sodium hydroxide solution, water
8. dry with materiala saline solution, dried over anhydrous sodium sulfate
9. concentrationconcentrated
10. customThe obtained crude product
11. customwas purified by silica gel column chromatography (elution solvent: ethyl acetate/methanol=1/0-4/1 gradient)
12. concentrationa desired fraction(s) was concentrated

ORD-Eintrag

ord-b4e613da362d4a50a73b0d94348033e9

Quelldatensatz

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07425634B2