Synthesis
General procedure for the synthesis of 6-oxo-1-phenyl-1,6-dihydro-pyridine-3-carboxylic acid from methyl 6-oxo-1-phenyl-1,6-dihydro-pyridine-3-carboxylate: at 0 °C, lithium hydroxide monohydrate (0.366 g, 8.73 mmol) was added to a mixed solution of tetrahydrofuran (9 mL) and water (6 mL) containing methyl 6-oxo-1-phenyl-1,6-dihydropyridine-3-carboxylate (1.0 g, 4.37 mmol) in a mixed solution of tetrahydrofuran (9 mL) and water (6 mL) and the reaction was stirred for 1 hour. After completion of the reaction, the reaction mixture was diluted with water and washed with ethyl acetate. Subsequently, the pH of the aqueous layer was adjusted to 2 with 2N hydrochloric acid and the precipitate was collected by filtration to afford 6-oxo-1-phenyl-1,6-dihydropyridine-3-carboxylic acid as a brown solid (0.740 g, 79% yield). The melting point of the product was 256-263°C. The structure of the product was determined by 1H NMR (400 MHz, DMSO-d6) δ 6.53 (d, J = 9.4 Hz, 1H), 7.40-7.49 (m, 5H), 7.87 (dd, J = 2.5, 9.8 Hz, 1H), 8.23 (d, J = 2.5 Hz, 1H); IR (KBr) ν 3446, 1708, 1645, 1577, 1263, 1228 cm-1; MS 214 (M-1) for characterization.
References
[1] Archiv der Pharmazie, 2013, vol. 346, # 9, p. 654 - 666
[2] Patent: US2008/319026, 2008, A1. Location in patent: Page/Page column 22
[3] Patent: WO2012/122165, 2012, A2. Location in patent: Page/Page column 63-64
[4] Patent: US2013/317059, 2013, A1. Location in patent: Paragraph 0042-0043
[5] Journal of Medicinal Chemistry, 2013, vol. 56, # 12, p. 5079 - 5093
