66684-60-4

82419-26-9

74-88-4

66684-60-4

General procedure for the synthesis of 2,3-difluoro-6-nitroanisole from 2,3-difluoro-6-nitrophenol and iodomethane: Intermediate B92: 3-fluoro-4-[4-(1-methylethyl)-1-piperazinyl]-2-(methoxy)aniline. Step A/Intermediate B93: 1,2-difluoro-3-(methoxy)-4-nitrobenzene. To a solution of 2,3-difluoro-6-nitrophenol (15.01 g, 85.8 mmol) in anhydrous dimethylformamide (120 mL) was sequentially added potassium carbonate (16.6 g, 120 mmol) and iodomethane (6.63 mL, 107 mmol). The reaction mixture was stirred at room temperature overnight. On the following day, the reaction mixture was poured into water and extracted twice with ether. The organic layers were combined, washed twice with 5% lithium chloride aqueous solution and dried over anhydrous sodium sulfate. The solvent was removed by concentration under reduced pressure to give 1,2-difluoro-3-(methoxy)-4-nitrobenzene as a yellow oil (14.7 g, 91% yield). 1H NMR (400 MHz, CDCl3) δ ppm: 4.13 (s, 3H), 7.00 (td, J = 9.07, 7.15 Hz, 1H), 7.67 (ddd, J = 9.35, 5.32, 2.20 Hz, 1H).