Synthesis
5-Chloropyridine-2-carboxylic acid (1.0 g, 6.35 mmol) was used as a raw material and it was mixed with concentrated HCl. H2SO4 (0.1 ml) and EtOH (10 ml) were added to the mixture and the reaction was subsequently heated at 80 °C for 16 hours. After completion of the reaction, the reaction mixture was cooled and concentrated under reduced pressure. The concentrated residue was dissolved in EtOAc (50 ml) and washed sequentially with saturated NaHCO3 solution (25 ml) and brine (25 ml). The organic phase was dried over MgSO4, filtered and concentrated under reduced pressure to afford the target compound ethyl 5-chloropyridinecarboxylate (990 mg, 84% yield).LCMS analysis showed the calculated value of MH+ to be 186; the measured value was 98% (MH+) m/z 186 with retention time Rt=1.13 min.1H NMR (250 MHz, CDCl3) δ ppm: 8.63-8.76 (1H, m), 8.10 (1H, d, J=8.4Hz), 7.82 (1H, dd, J=8.5,2.4Hz), 4.49 (2H, q, J=7.2Hz), 1.45 (3H, t, J=7.2Hz).
References
[1] Journal of Medicinal Chemistry, 2018, vol. 61, # 8, p. 3516 - 3540
[2] Patent: WO2009/135842, 2009, A1. Location in patent: Page/Page column 76
[3] Chemistry - A European Journal, 2014, vol. 20, # 13, p. 3610 - 3615
[4] Patent: WO2004/14902, 2004, A2. Location in patent: Page 42
[5] Patent: US2011/237791, 2011, A1. Location in patent: Page/Page column 66
