Hydrochloric Acid → 2-(Difluoromethoxy)-N-methoxy-N-methyl-3-pyridinecarboxamide

HRID 1690176Notes

Reaction equation

HRID 1690176 reaction equation
[CH3:1][O:2][N:3]([CH3:13])[C:4](=[O:12])[C:5]1[CH:10]=[CH:9][CH:8]=[N:7][C:6]=1[OH:11].Cl[C:15]([F:20])([F:19])C([O-])=O.[Na+].[OH-].[Na+].Cl>O.CN(C)C=O>[CH3:1][O:2][N:3]([CH3:13])[C:4](=[O:12])[C:5]1[CH:10]=[CH:9][CH:8]=[N:7][C:6]=1[O:11][CH:15]([F:20])[F:19]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 2734985Sodium chlorodifluoroacetateHCID 178502672HCID 178502672, compound

Product 1

HCID 866394092-(Difluoromethoxy)-N-methoxy-N-methyl-3-pyridinecarboxamideYield 53.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

N-methoxy-N-methyl-2-hydroxynicotinamide (500 mg, 2.76 mmol), sodium chlorodifluoroacetate (505 mg, 3.31 mmol), and sodium hydroxide (132 mg, 3.31 mmol) were added to N,N-dimethylformamide (1.4 mL). The resultant mixture was stirred at 125° C. overnight under an argon atmosphere. The reaction solution was cooled down to room temperature, added with 1N hydrochloric acid and water, and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, concentrated in vacuo, and purified using preparative thin-layer chromatography (chloroform/methanol=9/1). N-methoxy-N-methyl-2-difluoromethoxynicotinamide (341 mg, yield 53%) was obtained as a yellow oil.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. custompurified

Sources & evidence

ORD record
ord-e4dd9a58e3b047ec9e54933ba1947e39
Source dataset
uspto-grants-2012_04
Patent number
US08153634B2

Reaction notes

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