Synthesis
Suzuki coupling reaction was carried out in Biotage Smith Synthesizer using 6-bromo-2-pyridine carboxylic acid (202 mg, 1 mmol) and 4-tolylboronic acid (163 mg, 1.2 mmol). The reactants were mixed with Pd(PPh3)4 (25 mg) catalyst, saturated aqueous NaHCO3 solution (3 mL) and DME (3 mL) and reacted in a microwave reactor for 2 hours at 100 °C. The reaction progress was monitored by TLC, and after confirming the completion of the reaction, the reaction mixture was filtered and washed sequentially with water (2 × 50 mL) and ether (2 × 50 mL). After separating the organic and aqueous layers, the pH of the aqueous layer was adjusted with 1N HCl aqueous solution to about 1. Subsequently, the aqueous layer was extracted with ethyl acetate (3 × 60 mL). The organic layers were combined, dried with anhydrous sodium sulfate and filtered. Finally, the target product 6-(4-methylphenyl)-2-pyridinecarboxylic acid (191 mg, 90% yield) was obtained by evaporating the solvent.
References
[1] Patent: WO2011/94890, 2011, A1. Location in patent: Page/Page column 122
[2] Patent: US2012/4198, 2012, A1. Location in patent: Page/Page column 33-34
