2,4-Difluorophenol → Methyl 6-(2,4-Difluorophenoxy)nicotinate

HRID 552571Notes

Reaction equation

HRID 552571 reaction equation
[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][C:7](Cl)=[N:6][CH:5]=1.[F:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[OH:20].O.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][C:7]([O:20][C:14]2[CH:15]=[CH:16][C:17]([F:19])=[CH:18][C:13]=2[F:12])=[N:6][CH:5]=1

Participants

5

Reactant 3

HCID 1230512,4-DifluorophenolHCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 21835276Potassium carbonate hydrate

Product 1

HCID 59786749Methyl 6-(2,4-Difluorophenoxy)nicotinate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In Scheme D, Ra, Ra′, Rc, Rc′, Re, Rg and X are as previously defined. In Scheme D (step 1), the halide can be displaced by either a nucleophilic aromatic substitution or transition metal catalyzed reaction. For example, methyl-6-chloronicotinate and 2,4-difluorophenol is dissolved in a suitable solvent such as DMF. To the reaction mixture is added a suitable base such as potassium carbonate monohydrate and the heated at reflux for a period of 2 to 18 hours to yield [6-(2,4-Difluoro-phenoxy)-nicotinic acid methyl ester. The reaction is concentrated and purified according to techniques well known in the art. These resulting esters formed in Scheme E, Step 1 can be further elaborated to final compounds using the procedures described in Scheme B, step 2 and 3.

Workup

  1. temperaturethe heated
  2. temperatureat reflux for a period of 2 to 18 hours

Sources & evidence

ORD record
ord-45a34a03ad9b48ed9abbd7e952d97932
Source dataset
uspto-grants-2011_05
Patent number
US07951826B2

Reaction notes

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