Reaktion #59883

Reaktionsgleichung

sodium hydroxide

4-(5,9-dioxaspiro[3.5]non-7-yloxy)-2,3-dimethylpyridine 1-oxide

acetic anhydride

ammonium chloride

triethylamine

→

title compound

Ausbeute 50.4%

(4-(5,9-dioxaspiro[3.5]non-7-yloxy)-3-methylpyridin-2-yl)methanol

Ausbeute 50.4%

Lösungsmittel

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturit was cooled to 0° C
2. 2
   workup.STIRRINGthe mixture was stirred for one hour
3. 3
   workup.STIRRINGstirred at room temperature for another one hour
4. 4
   workup.STIRRINGAfter stirred at 50° C. for 2 hours
5. 5
   Einengenthe reaction mixture was concentrated
6. 6
   Sonstigethe residue was purified by silica gel column chromatography (NH silica gel, elution solvent: ethyl acetate/heptane=1/3)
7. 7
   workup.STIRRINGthe reaction mixture was stirred at room temperature for one hour
8. 8
   Einengenconcentrated
9. 9
   ExtraktionThe resultant residue was extracted with ethyl acetate three times
10. 10
    Waschenwashed with a saturated saline solution
11. 11
    Trocknendried over anhydrous sodium sulfate
12. 12
    Filtrationfiltered
13. 13
    Einengenconcentrated

Vorschrift

The 4-(5,9-dioxaspiro[3.5]non-7-yloxy)-2,3-dimethylpyridine 1-oxide (1.25 g, 4.71 mmol) obtained in the step (9f) was mixed with acetic anhydride (4.45 ml, 47.1 mmol). After the mixture was stirred at room temperature for one hour, it was cooled to 0° C. After triethylamine (656 μl, 4.71 mmol) was added, the mixture was stirred for one hour and stirred at room temperature for another one hour. After stirred at 50° C. for 2 hours, the reaction mixture was concentrated and the residue was purified by silica gel column chromatography (NH silica gel, elution solvent: ethyl acetate/heptane=1/3). To the obtained product, methanol (30 ml) and a 5N aqueous sodium hydroxide solution (2.24 ml, 11.2 mol) were added, and the reaction mixture was stirred at room temperature for one hour. A saturated aqueous solution of ammonium chloride was added to the reaction mixture to adjust the pH of the solution to about 9 and thereafter concentrated. The resultant residue was extracted with ethyl acetate three times. Organic layers were combined, washed with a saturated saline solution, dried over anhydrous sodium sulfate, filtered and concentrated to obtain the title compound (630 mg, yield: 49.6%) as a light yellow oil.

Quelle