Synthesis
1. 3,5-difluoroanisole (30 g, 208 mmol) was dissolved in 260 mL of dichloromethane at 0 °C. 2. Fuming nitric acid (60 mL) at a concentration of greater than 90% was added slowly and dropwise to the above solution. 3. The reaction mixture was kept stirred at 0 °C for 3 h. 4. After completion of the reaction, the reaction mixture was washed with water. 5. The aqueous phase was extracted with dichloromethane. 6. The organic phases were combined and washed with brine, followed by drying with magnesium sulfate.7. The dried organic phase was concentrated on a rotary evaporator.8. The residue was recrystallized by solvent mixing of hexane and ethyl acetate to afford 28.5 g (72% yield) of 1,5-difluoro-3-methoxy-2-nitrobenzene, the product being an off-white powder.1H NMR (400 MHz, DMSO) δ ppm: 7.20 (m, 2H), 3.91 (s, 3H).
References
[1] Patent: US2009/143367, 2009, A1. Location in patent: Page/Page column 30
[2] Journal of Medicinal Chemistry, 2011, vol. 54, # 21, p. 7621 - 7638
