Synthesis
General procedure for the synthesis of 4-methoxy-5-nitropyridin-2(1H)-one from 4-methoxy-3-nitropyridine: 250 mL of anhydrous THF was added to a 1 L flask, cooled to -78 °C, and then concentrated NH3 (100-150 mL). Solid t-BuOK (200 mmol, 22.5 g) was added to THF and stirred vigorously for 10 min until completely dissolved. In another 500 mL flask, 4-methoxy-3-nitropyridine (12.3 g, 80 mmol) was dissolved in 100 mL of anhydrous THF and cooled to 0°C. To this solution was added t-BuOOH (88 mmol, 16 mL). The t-BuOOH/THF solution was then slowly added to an ammonia solution at -78 °C via a dropping funnel over 20 min. The reaction mixture was slowly warmed to -40 °C and stirred at this temperature for 1 hour. Upon completion of the reaction, the reaction was quenched with saturated NH4Cl solution (20 mL) and the cooling bath was removed. The reaction mixture was stirred overnight at room temperature. The precipitate was collected by filtration and dried under vacuum to give a tan solid product (9.5 g, 70% yield). lC/MS analysis showed m/z 171 [M+H]+ as a single component.
References
[1] Journal of Medicinal Chemistry, 2007, vol. 50, # 1, p. 2 - 5
[2] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 5, p. 1508 - 1511
[3] Patent: WO2006/113837, 2006, A2. Location in patent: Page/Page column 36; 62-63
[4] ACS Medicinal Chemistry Letters, 2015, vol. 6, # 1, p. 42 - 46
[5] Patent: WO2005/37197, 2005, A2. Location in patent: Page/Page column 94
