Methanol → 2,6-Difluoro-nicotinic acid methyl ester

HRID 1396153Notes

Reaction equation

HRID 1396153 reaction equation
[F:1][C:2]1[N:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].CO.S(=O)(=O)(O)O.[C:19](=O)([O-])[O-].[K+].[K+]>O>[CH3:19][O:5][C:4](=[O:6])[C:3]1[CH:7]=[CH:8][C:9]([F:11])=[N:10][C:2]=1[F:1]

Participants

6

Reactant 4

HCID 887MethanolHCID 1118Sulfuric AcidHCID 11430Potassium CarbonateHCID 105830702,6-Difluoropyridine-3-carboxylic acid

Product 1

HCID 108449402,6-Difluoro-nicotinic acid methyl ester

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

In a round bottom flask, 2,6-difluoro-nicotinic acid (51, 5.60 g, 35.2 mmol), 60.0 mL of methanol and sulfuric acid (1.0 mL, 19.0 mmol) are combined and heated to reflux overnight. The reaction is poured into water, adjusted to pH around 9 with 1M aqueous potassium carbonate, and extracted with ethyl acetate. The organic layer is dried over sodium sulfate, filtered and the filtrate concentrated under vacuum to provide the desired compound as a yellow oil (52, 3.5 g).

Workup

  1. temperatureheated
  2. temperatureto reflux overnight
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer is dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under vacuum

Sources & evidence

ORD record
ord-1438f424cf3c49b3b4763e519a795088
Source dataset
uspto-grants-2014_12
Patent number
US08901118B2

Reaction notes

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