Synthesis
Step A: 5-bromopyridine-2-carboxylic acid (57, 1.0 g, 5.0 mmol) was dissolved in a solvent mixture of ethylene glycol dimethyl ether (12 mL) and water (4 mL). Subsequently, 4-fluorophenylboronic acid (17, 1.0 g, 7.5 mmol), anhydrous potassium carbonate (1.0 g, 7.5 mmol) and tetrakis(triphenylphosphine)palladium (289 mg, 0.25 mmol) were added sequentially. The reaction mixture was stirred at 98 °C for 24 h under nitrogen protection. After the completion of the reaction was monitored by thin layer chromatography (TLC), the reaction solution was cooled to room temperature. Water (40 mL) was added to the reaction solution and the pH was adjusted to 2-3 with 6 M hydrochloric acid solution. the precipitate was collected by filtration, the filter cake was redissolved in dichloromethane, and the organic layer was separated and washed with water. The aqueous phase was again adjusted to pH 2-3 with 6 M hydrochloric acid solution and the solid product was collected by filtration. The filter cake was washed with water to neutral and dried to give the crude product. The crude product was treated with 20 mL of saturated sodium bicarbonate solution to give the final target compound 5-(4-fluorophenyl)pyridine-2-carboxylic acid (61,942 mg) in 87.7% yield.
References
[1] Patent: CN108623532, 2018, A. Location in patent: Paragraph 0206; 0207; 0208
[2] Patent: EP1657242, 2006, A1. Location in patent: Page/Page column 31
[3] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 4, p. 812 - 819
[4] Medicinal Chemistry, 2017, vol. 13, # 2, p. 176 - 185
[5] Medicinal Chemistry Research, 2018, vol. 27, # 2, p. 374 - 387
