Methyl 3-methoxypyridine-2-carboxylate → (3-Methoxypyridin-2-yl)methanol

HRID 911428Notes

Reaction equation

HRID 911428 reaction equation
[CH3:1][O:2][C:3]1[C:4]([C:9](OC)=[O:10])=[N:5][CH:6]=[CH:7][CH:8]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[OH:10][CH2:9][C:4]1[C:3]([O:2][CH3:1])=[CH:8][CH:7]=[CH:6][N:5]=1

Participants

4

Reactant 2

HCID 20474189Methyl 3-methoxypyridine-2-carboxylateHCID 21226445Aluminium lithium hydride

Product 1

HCID 5324774(3-Methoxypyridin-2-yl)methanolYield 18%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Heat a mixture of 3-hydroxypicolinic acid (5.3 g, 38 mmol), potassium carbonate (15.8 g, 114 mmol), and iodomethane (9.6 mL, 153 mmol) in acetone (100 mL) and DMF (10 mL) overnight at 60° C. Cool the reaction mixture to ambient temperature, pour into brine, extract three times with ethyl ether, dry over anhydrous MgSO4 and concentrate in vacuo. Pass through a short plug of silica gel eluting with ether to provide 3-methoxy-2-methoxycarbonylpyridine as a pale yellow liquid (6.3 g, 100%). To a solution of 3-methoxy-2-methoxycarbonyl-pyridine (2.34 g, 14.0 mmol) in dry THF (25 mL) add slowly with stirring a solution of 1M lithium aluminum hydride in THF (10 mL, 10 mmol) and continue stirring overnight at ambient temperature. Quench cautiously with sodium sulfate decahydrate, filter under suction and rinse the solids with additional THF. Concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (3:1) to provide the desired intermediate as a white solid (350 mg, 18%).

Workup

  1. customQuench cautiously with sodium sulfate decahydrate
  2. filtrationfilter under suction
  3. washrinse the solids with additional THF
  4. concentrationConcentrate in vacuo
  5. customPurify by chromatography on silica gel eluting with hexane/EtOAc (3:1)

Sources & evidence

ORD record
ord-8c0e91de554a40048bb82ce6bf3e869b
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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