Synthesis
General procedure for the synthesis of 2-ethyl-5-bromopyridine from 2,5-dibromopyridine and diethylzinc: A suspension of 2,5-dibromopyridine (10 g, 42.21 mmol) and tetrakis(triphenylphosphine)palladium (Pd(PPh3)4, 2.43 g, 2.11 mmol) in tetrahydrofuran (THF, 100 mL) was slowly added to a suspension of 1 M diethyl Zinc (Et2Zn, 42.2 mL, 42.21 mmol). The reaction mixture was stirred at 0 °C for 30 min, then warmed up to room temperature and continued stirring for 1 h. The reaction was completed with saturated carbon dioxide. Upon completion of the reaction, the reaction was quenched with saturated sodium bicarbonate (NaHCO3) solution and extracted with ethyl acetate (EtOAc). The combined organic layers were washed sequentially with water and saturated saline, dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography with 4% ethyl acetate/petroleum ether as eluent to afford 5-bromo-2-ethylpyridine as a light yellow liquid (3 g, 38% yield). Thin layer chromatography (TLC) Rf value was 0.6 (10% ethyl acetate/petroleum ether).1H NMR (400MHz, CDCl3): δ 8.57 (d, J=2.4Hz, 1H), 7.72-7.69 (m, 1H), 7.06 (d, J=8.0Hz, 1H), 2.81-2.75 (m, 2H), 1.29 (t, J= 8.0 Hz, 3H).
References
[1] Patent: WO2015/36759, 2015, A1. Location in patent: Page/Page column 198
[2] Patent: US2014/275182, 2014, A1. Location in patent: Paragraph 0374; 0375
[3] Patent: US8912227, 2014, B1. Location in patent: Page/Page column 74
[4] Patent: WO2015/134038, 2015, A1. Location in patent: Page/Page column 90
