Cesium fluoride → 3-(4'-Chloro-4-ethyl-2'-fluorobiphen-3-yl)bicyclo[3.2.2]non-6-ene-2,4-dione

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A solution of 3-(5-bromo-2-ethylphenyl)bicyclo[3.2.2]non-6-ene-2,4-dione (0.180 g, 0.54 mmol) and 4-chloro-2-fluorophenylboronic acid (0.133 g, 0.76 mmol) in anhydrous dimethoxyethane (5 ml) is stirred at room temperature under an atmosphere of nitrogen. The reaction mixture is then evacuated and flushed with nitrogen (degassing cycle repeated 4 times). Cesium fluoride (0.246 g, 1.62 mmol) is added, and the suspension is stirred at room temperature for 45 minutes. Next [1,1′-bis(diphenylphosphino)ferrocene]dichloro-palladium(II) (0.066 g, 0.081 mmol) is added in one portion, and the reaction mixture is heated at 80° C. for 21.5 hours. After cooling to room temperature the suspension is filtered through diatomaceous earth, then washed with 2M hydrochloric acid (20 ml) and dichloromethane (20 ml). The organic phase is separated, and the aqueous phase is extracted with dichloromethane (10 ml×2). All organics are combined, dried over magnesium sulfate, filtered and the filtrate concentrated under reduced pressure to give a brown gum. The crude product is purified by flash column chromatography on silica gel (100% to 0% hexane/ethyl acetate eluant ratio), then further purified by preparative reverse-phase HPLC to afford 3-(4′-chloro-4-ethyl-2′-fluorobiphen-3-yl)bicyclo[3.2.2]non-6-ene-2,4-dione.

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