Synthesis
The general procedure for the synthesis of 4-(3-fluorophenyl)-2,2-dimethyl-5-(4-(methylthio)phenyl)furan-3(2H)-one from 2-bromoisobutyryl bromide and 2-(3-fluorophenyl)-1-(4-(methylthio)phenyl)ethanone was as follows: 2.60 g (10 mmol) of 2-(3-fluorophenyl)-1-(4-(methylthio)phenyl)ethanone was mixed with a 20.8 mL of N,N-dimethylacetamide was stirred and cooled to 0 °C. 2.0 g (50 mmol) of 60% sodium hydride was slowly added at 0 to 5°C and kept at this temperature and stirred for 1.0 hour. 1.38 g (20 mmol) of 1,2,4-triazole was dissolved in 13.8 mL of N,N-dimethylacetamide, then 2.29 g (10 mmol) of 2-bromoisobutyryl bromide was added dropwise, and the mixture was stirred for 2 hr. at about 30 °C. After completion of the reaction, the insoluble material was removed by filtration. The filtrate was slowly dripped into the reaction flask, taking about 1.0 hour. The mixture was stirred overnight at room temperature. Subsequently, 60 mL of 2N hydrochloric acid was added and the mixture was concentrated to near dryness. To the residue, 60 mL of water was added, filtered, and the filter cake was washed twice with water and finally recrystallized from ethanol to give 2.85 g of the target product in 86.8% yield.
References
[1] Patent: CN106866558, 2017, A. Location in patent: Paragraph 0102; 0103; 0104
[2] Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 4, p. 1137 - 1142
