2-Methyl-5-hydroxypyridine → 5-Methoxy-2-methylpyridine

HRID 900434Notes

Reaction equation

HRID 900434 reaction equation
[OH:1][C:2]1[CH:3]=[N:4][C:5]([CH3:8])=[CH:6][CH:7]=1.[CH3:9][O-].[Na+]>[Cl-].C1([N+](C)(C)C)C=CC=CC=1.CN(C)C=O>[CH3:9][O:1][C:2]1[CH:3]=[N:4][C:5]([CH3:8])=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 142752-Methyl-5-hydroxypyridineHCID 10942334Sodium Methoxide

Product 1

HCID 133587775-Methoxy-2-methylpyridine

Reagents, catalysts & solvents 2

HCID 67309Phenyltrimethylammonium chlorideCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 3-hydroxy-6-methylpyridine (2.5 g), sodium methoxide (1.36 g) and phenyltrimethylammonium chloride (4.33 g) in dry dimethylformamide (25 ml) was heated at reflux under argon for 2.5 h. The mixture was allowed to cool then stirred at room temperature overnight. Insoluble material was removed by filtration and washed with ethanol. The filtrate was acidified with 6M hydrochloric acid and the solvent was removed in vacuo. The residue was then diluted with water, basified with 2M sodium hydroxide and extracted with ether. The combined extracts were washed with brine, dried (MgSO4), filtered and evaporated. The crude product was purified by column chromatography on silica gel eluting with 3% ethyl acetate in hexane (1.55 g, 55%).

Workup

  1. temperatureat reflux under argon for 2.5 h
  2. temperatureto cool
  3. customInsoluble material was removed by filtration
  4. washwashed with ethanol
  5. customthe solvent was removed in vacuo
  6. additionThe residue was then diluted with water
  7. extractionextracted with ether
  8. washThe combined extracts were washed with brine
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. customevaporated
  12. customThe crude product was purified by column chromatography on silica gel eluting with 3% ethyl acetate in hexane (1.55 g, 55%)

Sources & evidence

ORD record
ord-f899df62487a4d41b7ccfc6fee038241
Source dataset
uspto-grants-2008_04
Patent number
US07358376B2

Reaction notes

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