Methanol → Methyl 2-chloropyridine-4-carboxylate

HRID 1635508Notes

Reaction equation

HRID 1635508 reaction equation
S(Cl)(Cl)=O.[Cl:5][C:6]1[CH:11]=[C:10]([C:12]([OH:14])=[O:13])[CH:9]=[CH:8][N:7]=1.[CH3:15]O.[OH-].[Na+]>C1(C)C=CC=CC=1.O>[CH3:15][O:13][C:12](=[O:14])[C:10]1[CH:9]=[CH:8][N:7]=[C:6]([Cl:5])[CH:11]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 24386Thionyl ChlorideHCID 2369852-Chloroisonicotinic acid

Product 1

HCID 2736842Methyl 2-chloropyridine-4-carboxylateYield 73.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a solution of thionyl chloride (13.85 mL, 190.38 mmol) in toluene (50 mL) was added 2-chloropyridine-4-carboxylic acid (15 g, 95 mmol). The solution was heated to reflux for 3 hours. The resulting brown color solution was cooled to room temperature, and methanol (11.56 mL, 285.6 mmol) was added slowly dropwise. The mixture was brought to reflux for 15 minutes and became clear. The solution was then cooled to room temperature and poured into water (150 mL), basified with 50 percent sodium hydroxide and extracted with ethyl acetate (2×200 ml). The organic layer was separated and washed with brine, dried with magnesium sulfate, filtered and concentrated to yield the titled compound (11.93 g, 73%) as a brown color solid. This was used in the next step without further purification.

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux for 3 hours
  3. temperatureto reflux for 15 minutes
  4. temperatureThe solution was then cooled to room temperature
  5. extractionextracted with ethyl acetate (2×200 ml)
  6. customThe organic layer was separated
  7. washwashed with brine
  8. dry with materialdried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-56eee50d56ee46a9b46482e7e1bf7606
Source dataset
uspto-grants-2003_01
Patent number
US06509361B1

Reaction notes

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