Synthesis
Example 19 Preparation of 3-fluoro-4-nitropyridine N-oxide (3-3): refer to the literature method of Bellas and Suschitzky (Chem. Soc., 1965, 2096-2100). Fuming nitric acid (21 mL) was added slowly and dropwise at 120°C to a stirred solution of 3-fluoropyridine N-oxide (3-2) (10.4 g, 90 mmol) dissolved in sulfuric acid (52 mL) over a period of 1 hour. After the dropwise addition, the reaction mixture was continued to be stirred at 120 °C for 3 hours. Subsequently, the reaction solution was cooled to room temperature and carefully poured into ice (300 mL). The pH of the mixture was adjusted to 7 with 20% sodium hydroxide solution, followed by extraction with chloroform. The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was recrystallized by mixed ether/hexane solvent to give a light yellow solid product (7.5 g, 51% yield).1H NMR (400 MHz, CDCl3): δ 8.05 (m, 2H), 8.22 (m, 1H).
References
[1] Patent: US2003/92679, 2003, A1
[2] Bioorganic and Medicinal Chemistry Letters, 1996, vol. 6, # 3, p. 333 - 338
[3] Patent: US2007/167442, 2007, A1. Location in patent: Page/Page column 42
[4] Patent: US2004/14742, 2004, A1. Location in patent: Page 32
[5] Patent: WO2013/184757, 2013, A1. Location in patent: Page/Page column 85; 86
