Synthesis
(a) Preparation of ethyl 5-bromopyridine-2-carboxylate 2: Thionyl chloride (5 mL) was added slowly and dropwise to a suspension of 5-bromopyridine-2-carboxylic acid 1 (2.02 g, 10 mmol) in 50 mL of anhydrous ethanol. The reaction mixture was stirred at room temperature for 18 hours. After completion of the reaction, the solvent was removed by distillation under reduced pressure, and the resulting crude product was purified by column chromatography (eluent: hexane/ethyl acetate, 2:1, v/v) to afford ethyl 5-bromopyridine-2-carboxylate 2 (2.3 g, quantitative yield) as a colorless oil.1H NMR (CDCl3) δ (ppm): 8.80 (d, J = 1.6 Hz, 1H), 8.00 (dd, J = 8.4, 2.0 Hz, 1H), 7.90 (d, J=8.4 Hz, 1H), 4.50 (q, J=7.2 Hz, 2H), 1.44 (t, J=7.2 Hz, 3H).
References
[1] Patent: WO2012/76898, 2012, A1. Location in patent: Page/Page column 58
[2] Patent: EP2471789, 2012, A1. Location in patent: Page/Page column 115
[3] Patent: US2005/113374, 2005, A1. Location in patent: Page/Page column 8; 12-13
[4] Heterocycles, 1981, vol. 15, # 1, p. 213 - 223
[5] Patent: WO2009/5645, 2009, A1. Location in patent: Page/Page column 153