Hydrochloric Acid → 2-Chloro-5-fluoro-6-methoxynicotinic acid

HRID 15128Notes

Reaction equation

HRID 15128 reaction equation
[Cl:1][C:2]1[C:7]([C:8]([OH:10])=[O:9])=[CH:6][C:5]([F:11])=[C:4](Cl)[N:3]=1.[CH3:13][O-:14].[Na+].O.Cl>CO>[Cl:1][C:2]1[C:7]([C:8]([OH:10])=[O:9])=[CH:6][C:5]([F:11])=[C:4]([O:14][CH3:13])[N:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 27336592,6-Dichloro-5-fluoronicotinic acidHCID 10942334Sodium Methoxide

Product 1

HCID 455882302-Chloro-5-fluoro-6-methoxynicotinic acidYield 65%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution of 2,6-dichloro-5-fluoro-3-pyridinecarboxylic acid (51.12 g, 243 mmol) in methanol (400 ml) was treated with sodium methoxide in methanol (25% w/v, 100 ml, 535 mmol) and the mixture heated to reflux for 4 hours. The cooled mixture was treated with water (400 ml) and acidified to pH2 with aqueous hydrochloric acid (2M) then concentrated to ca 400 ml. Filtration, washing with water and drying in vacuo over P2O5 for 18 h afforded the product as a white solid (32.65 g, 65%).

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 4 hours
  3. concentrationthen concentrated to ca 400 ml
  4. filtrationFiltration
  5. washwashing with water
  6. dry with materialdrying in vacuo over P2O5 for 18 h

Sources & evidence

ORD record
ord-a158cf89896e435dbf8220d1c6c239ba
Source dataset
uspto-grants-2010_06
Patent number
US07732460B2

Reaction notes

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