The general procedure for the synthesis of 3-fluoro-4-methylanisole from 5-methoxy-2-methylaniline was as follows: a mixed system of 5-methoxy-2-methylaniline (5.0 g; 36 mmol), concentrated hydrochloric acid (7.6 mL, 12 M solution; 91 mmol), and deionized water (11 mL) was heated and stirred at 60 °C for 15 min until complete dissolution. After the reaction solution was cooled to 0 °C, aqueous sodium nitrite (2.5 g; 36 mmol) was slowly added dropwise to control the internal temperature ≤7 °C. The reaction solution was then stirred at 0 °C for 15 min. The reaction solution was continued to be stirred at 0 °C for 30 min, followed by cautious addition of pre-cooled tetrafluoroboric acid solution (5.3 mL, 48% solution; 40 mmol). The reaction mixture was stirred at 0 °C for 20 min before the resulting brown solid was collected by filtration and washed sequentially with ice water (3 × 10 mL) and deionized water (2 × 10 mL). The solid was dried under high vacuum for 20 h. The solid was then heated with a heat gun until the release of white fumes of boron trifluoride was stopped. The resulting brown oil was extracted with ethyl acetate and water in liquid-liquid extraction, and the organic phase was dried with anhydrous sodium sulfate and concentrated under reduced pressure, and finally purified by short distillation to obtain the colorless oily product 3-fluoro-4-methylanisole (1.6 g; 31% yield).
