Synthesis
General procedure for the synthesis of 2,4-difluoro-5-nitrobenzonitrile from 2,4-difluorobenzonitrile: Potassium nitrate (16.4 g, 147.4 mmol) was slowly added to concentrated sulfuric acid (85 ml, 1582 mmol) at 0 °C, followed by 2,4-difluorobenzonitrile (11.0 g, 79.1 mmol) dropwise. The reaction mixture was stirred at this temperature for 4 hours. Upon completion of the reaction, the mixture was quenched by pouring into ice/water (800 mL). The precipitated solid product was collected by filtration and dried to give 2,4-difluoro-5-nitrobenzonitrile (13.8 g, 95% yield) as a white solid. The product was confirmed by NMR hydrogen spectrum (400 MHz, CDCl3): δ 8.48 (m, 1H), 7.24 (m, 1H).
References
[1] Patent: WO2006/87530, 2006, A1. Location in patent: Page/Page column 59
[2] Patent: WO2005/103010, 2005, A2. Location in patent: Page/Page column 40
[3] Patent: CN106854165, 2017, A. Location in patent: Paragraph 0106; 0107; 0138; 0139
[4] Journal of Medicinal Chemistry, 1994, vol. 37, # 4, p. 467 - 475
[5] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 15, p. 2019 - 2022
