Methanol → Methyl 2-chloro-3-methylpyridine-4-carboxylate

HRID 2238646Notes

Reaction equation

HRID 2238646 reaction equation
[Cl:1][C:2]1(C)[CH:7]=[C:6](I)[CH:5]=[CH:4][NH:3]1.[C:10](=[O:13])([O-])O.[Na+].CN(C)[CH:17]=[O:18].[C]=O.[CH3:22]O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[CH3:10][O:13][C:17](=[O:18])[C:6]1[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[C:7]=1[CH3:22]

Participants

9

Reactant 5

HCID 887MethanolHCID 6228DimethylformamideHCID 516892Sodium Bicarbonate2×HCID 86619137HCID 86619137, compoundHCID 178418416HCID 178418416, compound

Product 1

HCID 53436889Methyl 2-chloro-3-methylpyridine-4-carboxylate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 962WaterSolvent

Procedure

The mixture of 1.0 g of 2-chloro-4-iodo picoline, 84 mg of palladium acetate, 218 mg of 1,1′-bisdiphenylphosphino ferrocene, 990 mg of sodium hydrogen carbonate, 10 mL of N,N-dimethylformamide, and 10 ml of methanol, was stirred overnight in a carbon monoxide atmosphere at 80° C. After cooling the reaction mixture back to room temperature, water and a saturated aqueous solution of sodium hydrogen carbonate were added thereto, and extracted with ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. The insolubles were filtered, the filtrate was concentrated under reduced pressure, and then the obtained residue was purified by silica gel column chromatography to obtain 522 mg of 2-chloro-3-methylisonicotinic acid methyl ester [48-1] as a colorless oily product.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationThe insolubles were filtered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-64b96f4f0f7f4d75bc557dd1be8aafca
Source dataset
uspto-grants-2010_05
Patent number
US07718801B2

Reaction notes

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