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

HRID 31589Notes

Reaction equation

HRID 31589 reaction equation
[CH3:1][C:2]1[C:7]([CH3:8])=[C:6]([O:9][CH2:10][C:11]2([CH3:21])[O:20][CH2:19][C:14]3([O:18][CH2:17][CH2:16][O:15]3)[CH2:13][O:12]2)[CH:5]=[CH:4][N+:3]=1[O-].C(N(CC)CC)C.C(OC(=O)C)(=[O:32])C>>[CH3:8][C:7]1[C:2]([CH2:1][OH:32])=[N:3][CH:4]=[CH:5][C:6]=1[O:9][CH2:10][C:11]1([CH3:21])[O:20][CH2:19][C:14]2([O:18][CH2:17][CH2:16][O:15]2)[CH2:13][O:12]1

Participants

4

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 597925822,3-Dimethyl-4-((8-methyl-1,4,7,9-tetraoxaspiro[4.5]dec-8-yl)methoxy)pyridine 1-oxide

Product 1

HCID 59792595(3-Methyl-4-((8-methyl-1,4,7,9-tetraoxaspiro[4.5]dec-8-yl)methoxy)pyridin-2-yl)methanolYield 26.1%

Conditions

Temperature
50 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-b4e613da362d4a50a73b0d94348033e9
Source dataset
uspto-grants-2008_09
Patent number
US07425634B2

Reaction notes

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