General Description
2′,6′-Difluoroacetophenone undergoes ruthenium-catalyzed phenylation with phenylboronate via carbon-fluorine bond cleavage to yield 2′,6′-diphenylacetophenone.
Synthesis
GENERAL STEPS: Magnesium chloride (1.65 g, 17.3 mmol) was added to a solution of diethyl malonate (1.24 g, 7.7 mmol) in ethyl acetate (20 mL) and the mixture was stirred at room temperature for 30 minutes. Subsequently, triethylamine (2.35 mL, 16.7 mmol) was added and stirring was continued for 30 minutes. The reaction mixture was cooled to 0 °C and a solution of ethyl acetate (5 mL) of 2,6-difluorobenzoyl chloride (1.0 g, 5.6 mmol) was slowly added dropwise over a period of 15 min, ensuring that the internal temperature did not exceed 5 °C. After dropwise addition, the reaction mixture was returned to room temperature and stirred for 3 hours. Upon completion of the reaction, the reaction was quenched with 1N hydrochloric acid (50 mL) and extracted with ethyl acetate (100 mL). The organic phase was separated, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to give the intermediate (1.97 g) as a colorless oil. The oil was dissolved in acetonitrile (25 mL), water (2 mL) was added, and the solution was transferred to a pressure reactor and sealed. The mixture was heated to 150 °C and kept for 1 hour. At the end of the reaction, it was cooled to room temperature and the pressure was released. The yield of 2,6-difluoroacetophenone was determined to be 874 mg (100% yield) by HPLC weight analysis.
