Synthesis
The general procedure for the synthesis of 5-bromo-2-isopropoxypyridine from 2-iodopropane and 2-hydroxy-5-bromopyridine was as follows: with reference to Example 17, 5-bromo-2-isopropoxypyridine was prepared as follows: 5-bromopyridin-2(1H)-one (5 g, 28.7 mmol) and potassium carbonate (9.93 g, 71.8 mmol) were mixed in dimethyl sulfoxide. 2-Iodopropane (3.73 ml, 37.3 mmol) was slowly added to the reaction mixture at room temperature and stirred continuously at the same temperature for 4 hours. After completion of the reaction, the reaction solution was diluted with ethyl acetate and washed sequentially with water and saturated saline. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The resulting crude product was purified by silica gel column chromatography (eluent ratio: ethyl acetate/hexane = 20/80 to 50/50) to afford the target compound 5-bromo-2-isopropoxypyridine (4.72 g, 76% yield) as a colorless oil. Its 1H-NMR (400 MHz, CDCl3) data were as follows: δ1.33 (6H, d, J=6.3 Hz), 5.18-5.28 (1H, m), 6.59 (1H, d, J=8.8 Hz), 7.61 (1H, dd, J=8.8,2.9 Hz), 8.17 (1H, d, J=2.0 Hz).
References
[1] Patent: EP1892241, 2008, A1. Location in patent: Page/Page column 124
[2] ACS Medicinal Chemistry Letters, 2018, vol. 9, # 7, p. 761 - 767
[3] Patent: WO2005/123675, 2005, A1. Location in patent: Page/Page column 54
