Acetic Anhydride → (4-(5,7-Dioxaspiro[2.5]oct-6-ylmethoxy)-3-methylpyridin-2-yl)methanol

HRID 1645510Notes

Reaction equation

HRID 1645510 reaction equation
[CH2:1]1[C:3]2([CH2:8][O:7][CH:6]([CH2:9][O:10][C:11]3[CH:16]=[CH:15][N+:14]([O-])=[C:13]([CH3:18])[C:12]=3[CH3:19])[O:5][CH2:4]2)[CH2:2]1.C(OC(=O)C)(=[O:22])C.[OH-].[Na+]>>[CH2:1]1[C:3]2([CH2:8][O:7][CH:6]([CH2:9][O:10][C:11]3[CH:16]=[CH:15][N:14]=[C:13]([CH2:18][OH:22])[C:12]=3[CH3:19])[O:5][CH2:4]2)[CH2:2]1

Participants

4

Reactant 3

HCID 7918Acetic AnhydrideHCID 14798Sodium HydroxideHCID 597925884-(5,7-Dioxaspiro[2.5]oct-6-ylmethoxy)-2,3-dimethylpyridine 1-oxide

Product 1

HCID 59792562(4-(5,7-Dioxaspiro[2.5]oct-6-ylmethoxy)-3-methylpyridin-2-yl)methanolYield 28.9%

Conditions

Temperature
85 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-4ac6499926ec4cd08355ff90b527db40
Source dataset
uspto-grants-2012_02
Patent number
US08124780B2

Reaction notes

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