Synthesis
Under nitrogen protection, 2-bromo-4-pyridinecarboxylic acid (0.210 g, 1.040 mmol) was dissolved in degassed 1,2-dimethoxyethane (DME, 8 mL). Tetrakis(triphenylphosphine)palladium(0) (0.060 g, 0.052 mmol) was added to the solution and the reaction mixture was stirred for 15 minutes. Subsequently, aqueous potassium carbonate (4.16 mL, 8.32 mmol) and phenylboronic acid (0.171 g, 1.403 mmol) were added. The reaction mixture was refluxed at 95 °C for 18 h, after which it was cooled to room temperature. The reaction mixture was filtered through diatomaceous earth and the pH was adjusted to 3-4 with acid to precipitate a white precipitate, which was filtered and washed with water. The white powdery product 2-phenyl-pyridine-4-carboxylic acid was obtained by recrystallization from 2-methoxyethanol. Yield: 0.106 g, 57% yield. The product was characterized by 1H NMR (400 MHz, DMSO-d6): δ 7.44-7.60 (m, 3H), 7.71-7.86 (dd, J = 4.9, 1.5 Hz, 1H), 8.05-8.19 (m, 2H), 8.23-8.35 (t, J = 1.2 Hz, 1H), 8.79-8.93 (dd, J = 5.1, 0.8 Hz, 1H), 13.56-13.97 (s, 1H).UPLC-ESI analysis: retention time 1.37 min, m/z 200.5 [M + H]+ (purity 92%).
References
[1] Organic Letters, 2016, vol. 18, # 23, p. 6094 - 6097
[2] Patent: US2014/357650, 2014, A1. Location in patent: Paragraph 0456; 0457; 0458; 0459
[3] Journal of Medicinal Chemistry, 2014, vol. 57, # 7, p. 3053 - 3074
[4] Patent: WO2011/32269, 2011, A1. Location in patent: Page/Page column 34
[5] Patent: US2005/54627, 2005, A1. Location in patent: Page/Page column 44
