反应详情

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.

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