2-Chloroisonicotinic acid → Methyl 2-chloropyridine-4-carboxylate

HRID 429198Notes

Reaction equation

HRID 429198 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][N:3]=1.[C:11](=O)(O)[O-].[Na+]>CO>[CH3:11][O:9][C:8]([C:6]1[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[CH:7]=1)=[O:10]

Participants

4

Reactant 2

HCID 2369852-Chloroisonicotinic acidHCID 516892Sodium Bicarbonate

Product 1

HCID 2736842Methyl 2-chloropyridine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2-Chloropyridine-4-carboxylic acid (15.5 g, 98 mmol) was suspended in methanol (175 ml) and anhydrous hydrogen chloride gas was slowly bubbled through the reaction mixture while cooling in a methanol/water (20/80) dry ice bath. Bubbling was continued for 40 min. during which time the suspension cleared to a partial solution. Ice bath was removed and the reaction mixture was heated to reflux under anhydrous conditions for 30 min. to give a clear yellow solution. The solution was cooled in an ice bath and saturated sodium bicarbonate was slowly added with stirring till the pH was neutral. The organics were removed in vacuo and the product was extracted into ethyl acetate. The ethyl acetate layer was dried over sodium sulfate, filtered, and concentrated in vacuo to yield 2-chloropyridine-4-carboxylic acid methyl ester as a brown liquid.

Workup

  1. customanhydrous hydrogen chloride gas was slowly bubbled through the reaction mixture
  2. temperaturewhile cooling in a methanol/water (20/80) dry ice bath
  3. customBubbling
  4. customIce bath was removed
  5. temperaturethe reaction mixture was heated
  6. temperatureto reflux under anhydrous conditions for 30 min.
  7. customto give a clear yellow solution
  8. temperatureThe solution was cooled in an ice bath
  9. customThe organics were removed in vacuo
  10. extractionthe product was extracted into ethyl acetate
  11. dry with materialThe ethyl acetate layer was dried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-87687d4c73714469bd239037fda9337f
Source dataset
uspto-grants-2001_11
Patent number
US06316464B1

Reaction notes

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