Acetic Acid → METHYL 2-METHOXY-6-METHYLPYRIDINE-3-CARBOXYLATE

HRID 2177658Notes

Reaction equation

HRID 2177658 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[N:6][C:5]=1Cl.[Na].[C:14](O)(=[O:16])C>CO.C(OCC)(=O)C.O>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[N:6][C:5]=1[O:16][CH3:14]

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 5360545Sodium2×HCID 13055804Methyl 2-chloro-6-methylpyridine-3-carboxylate

Product 1

HCID 10910170METHYL 2-METHOXY-6-METHYLPYRIDINE-3-CARBOXYLATE

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent3×HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 2-chloro-6-methyl-nicotinic acid methyl ester (10.4 g, 56.52 mmol) in MeOH under nitrogen is added a solution of sodium (2.58 g, 113.04 mmol) in methanol (80.0 mL) (sodium metal is dissolved in methanol under a nitrogen atmosphere) at room temperature. The reaction mixture is refluxed overnight. The reaction is cooled to room temperature and the pH is adjusted to pH=7 with acetic acid. The reaction mixture is diluted with ethyl acetate (100 mL) and water (30 mL). The organic layer is separated and the aqueous layer is extracted with ethyl acetate (2×75 mL). The combined organic extracts are dried over Na2SO4, filtered, and concentrated to give crude product. Yield: 7.25 g (71%). 1H NMR (400 MHz, CDCl3), δ8.066-8.047 (d, J=7.6 Hz, 1H), 6.782-6.764 (d, J=7.2 Hz, 1-1H), 4.029 (s, 3H), 3.879 (s, 3H), 2.483 (s, 3H); ES/MS m/z 182.2 [M+H]+.

Workup

  1. temperatureThe reaction mixture is refluxed overnight
  2. customThe organic layer is separated
  3. extractionthe aqueous layer is extracted with ethyl acetate (2×75 mL)
  4. dry with materialThe combined organic extracts are dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give crude product

Sources & evidence

ORD record
ord-aaa03f6945f040bca35bd6002d079408
Source dataset
uspto-grants-2015_06
Patent number
US09067920B2

Reaction notes

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