1-Chloro-5-fluoro-2-methoxy-4-nitrobenzene

Synthesis

Potassium carbonate (18 g, 131 mmol) and iodomethane (8.0 mL, 131 mmol) were added to a solution of 2-chloro-4-fluoro-5-nitrophenol (5.0 g, 26.1 mmol) in acetone (100 mL) and stirred at room temperature. The reaction mixture was stirred at room temperature for 2 h. The progress of the reaction was monitored by thin layer chromatography (TLC). After completion of the reaction, the solvent was removed by evaporation under reduced pressure. The residue was diluted with distilled water (100 mL) and extracted with ethyl acetate (3 x 100 mL). The organic layers were combined, washed sequentially with distilled water (100 mL) and saturated saline (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 2-chloro-4-fluoro-5-nitroanisole as a yellow solid. Yield: 5.0 g (93%). 1H NMR (400 MHz, DMSO-d6): δ 7.94-7.97 (m, 1H), 7.81-7.83 (m, 1H), 3.95 (s, 3H).

References

[1] Patent: WO2018/37223, 2018, A1. Location in patent: Page/Page column 206; 207
[2] Patent: US5136868, 1992, A
[3] Patent: US4427438, 1984, A
[4] Patent: US2004/162282, 2004, A1
[5] Patent: US2009/143367, 2009, A1. Location in patent: Page/Page column 37-38