Synthesis
The general procedure for the synthesis of 1-(4-bromo-5-fluoro-2-hydroxyphenyl)ethanone using 3-bromo-4-fluorophenyl acetate as starting material was as follows: 3-bromo-4-fluorophenyl acetate (5.5 g, 23 mmol) was dissolved in boron trifluoride acetic acid complex (47 mL, 340 mmol), and the reaction was heated for 14 hours at 155 °C. Upon completion of the reaction, the reaction mixture was cooled to 0 °C and treated with ice water. After the ice bath was removed, the ice was allowed to melt naturally. Subsequently, the reaction mixture was diluted with cold water and filtered. The collected solid was washed with cold water and dried in air. The dried product was adsorbed on silica gel and purified by fast column chromatography with a gradient ratio of hexane/ethyl acetate (0%-30%) as eluent, resulting in the target product 1-(4-bromo-5-fluoro-2-hydroxyphenyl)ethanone (4.0 g, 73% yield). It is to be noted that no ionization signal was observed in mass spectrometry analysis for this product.
References
[1] Patent: WO2011/75630, 2011, A1. Location in patent: Page/Page column 107
[2] Patent: US2005/209274, 2005, A1. Location in patent: Page/Page column 42
[3] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 19, p. 4851 - 4856
[4] Patent: EP3381896, 2018, A1. Location in patent: Paragraph 0455
