Synthesis
Under ice bath conditions, 6.38 g (48 mmol) of aluminum trichloride and 40 mL of methylene chloride were added to a 100 mL round bottom flask and stirred until dissolved. Subsequently, 4.68 g (60 mmol) of acetyl chloride was slowly added, keeping the reaction temperature at 5 to 10 °C. Stirring was continued at 5°C for 10 minutes, followed by the slow dropwise addition of 5.04 g (40 mmol) 2-fluoroanisole. After the dropwise addition was completed, the reaction mixture was stirred at 5°C for 1 hour. Upon completion of the reaction, the mixture was carefully poured into 100 mL of ice water to quench the reaction. The aqueous layer was extracted with dichloromethane (2 x 30 mL) and the organic phases were combined. The organic phase was washed sequentially with water (2 x 30 mL), dried over anhydrous magnesium sulfate, filtered and concentrated. The crude product was washed with petroleum ether and finally recrystallized with ethyl acetate to obtain the target product 3-fluoro-4-methoxyacetophenone in 92.4% yield.
References
[1] Patent: CN107686465, 2018, A. Location in patent: Paragraph 0041; 0053; 0054
[2] Patent: US6342510, 2002, B1. Location in patent: Page column 28
[3] Patent: US5098602, 1992, A
[4] Patent: WO2006/136829, 2006, A2. Location in patent: Page/Page column 123
[5] Journal of Organic Chemistry, 1953, vol. 18, p. 910,914
