Methyl iodide → 5-Methoxy-2-methylpyridine

HRID 1995845Notes

Reaction equation

HRID 1995845 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:5]=[CH:6][C:7]([CH3:10])=[N:8][CH:9]=1.[CH3:11]I>CCCCCC.CN(C)C=O>[CH3:11][O:3][C:4]1[CH:5]=[CH:6][C:7]([CH3:10])=[N:8][CH:9]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 142752-Methyl-5-hydroxypyridineHCID 24758Sodium hydride

Product 1

HCID 133587775-Methoxy-2-methylpyridine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8058HexaneSolvent

Procedure

To sodium hydride (50% oil dispersion, 43.2 g, 21.6 g of active NaH, 900 mmol), prewashed in dry hexane, in 800 ml of dimethylformamide (DMF) is added 5-hydroxy-2-methylpyridine (98.8 g, 906 mmol) in 700 ml of DMF at 15° and over 0.75 hour. The reaction is allowed to warm to RT and is stirred for 2 hours. It is then cooled to 10°, and methyliodide is added over 0.5 hour. The reaction is again allowed to warm to RT and is stirred overnight. It is then filtered through celite, and the solid is washed with chloroform, filtered and rotoevaporated. The resulting solid is washed with chloroform 3X, and is stirred with chloroform overnight. It is filtered and rotoevaporated, after which ether is added, followed by 10% sodium hydroxide and water. The mixture is extracted with ether (3X). The combined ether extracts are washed with water and with brine, dried over calcium sulfate, filtered and rotoevaporated to give 5-methoxy-2 -methylpyridine.

Workup

  1. temperatureIt is then cooled to 10°
  2. temperatureto warm to RT
  3. stirringis stirred overnight
  4. filtrationIt is then filtered through celite
  5. washthe solid is washed with chloroform
  6. filtrationfiltered
  7. washThe resulting solid is washed with chloroform 3X
  8. stirringis stirred with chloroform overnight
  9. filtrationIt is filtered
  10. additionafter which ether is added
  11. extractionThe mixture is extracted with ether (3X)
  12. washThe combined ether extracts are washed with water and with brine
  13. dry with materialdried over calcium sulfate
  14. filtrationfiltered

Sources & evidence

ORD record
ord-c81f60af629b48fabd3ab0de048fc28e
Source dataset
uspto-grants-1983_09
Patent number
US04406689

Reaction notes

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