Methyl iodide → Methyl 3-methylpyridine-2-carboxylate

HRID 2041307Notes

Reaction equation

HRID 2041307 reaction equation
[CH3:1][C:2]1[C:3]([C:8]([OH:10])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.[C:11](=O)([O-])[O-].[K+].[K+].IC>CC(C)=O>[CH3:11][O:9][C:8]([C:3]1[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][N:4]=1)=[O:10]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 2687573-Methylpicolinic acid

Product 1

HCID 12264487Methyl 3-methylpyridine-2-carboxylateYield 57.1%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Heat a mixture of 3-methylpicolinic acid (1.0 g, 7.3 mmol), potassium carbonate (4.1 g, 29.7 mmol), and iodomethane (4.4 g, 31.0 mmol) in acetone (35 mL) overnight under reflux. Filter, wash the residue with EtOAc, and concentrate in vacuo. Pass through a short plug of silica gel eluting with hexane/EtOAc (1:1) to provide 2-methoxycarbonyl-3-methylpyridine as a pale yellow liquid (630 mg, 57%). To a solution of 2-methoxycarbonyl-3-methylpyridine in anhydrous THF (10 mL) at 0° C., add with stirring a solution of 1M lithium aluminum hydride in THF (5 mL, 5 mmol), and continue stirring for 30 min at 0° C. Allow the mixture to warm to ambient temperature and quench cautiously with 0.5M aqueous NaOH. Heat the mixture at 60° C. for 40 min, cool to ambient temperature, extract with EtOAc, dry over anhydrous Na2SO4 and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (4:3) to give the desired intermediate (90 mg, 18%).

Workup

  1. temperatureHeat
  2. temperatureunder reflux
  3. filtrationFilter
  4. washwash the residue with EtOAc
  5. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-8dff93381305465e830985cf57e3585e
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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