Citric Acid → 2-(Benzamido)-4-(2-(benzofuran-5-yl)ethyl)benzoic acid

Participants

Reaction Conditions

Reaction Steps

0.12 g of 5-bromobenzofuran, 0.20 g of cesium carbonate, 30 mg of tetrabutylammonium bromide and 48 mg of polymer supported di(acetato)dicyclohexylphenylphosphine palladium(II) were added to 2.0 mL of toluene solution containing 0.10 g of tert-butyl 2-(benzamido)-4-vinylbenzoate at room temperature and stirred at 110° C. for 24 hours. After the reaction mixture was cooled to room temperature, 48 mg of polymer supported di(acetato) dicyclohexylphenyl-phosphine palladium(II) was added and stirred at 110° C. for 24 hours. After the reaction mixture was cooled to room temperature, ethyl acetate and 10% citric acid aqueous solution were added. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with 10% citric acid aqueous solution and a saturated sodium chloride aqueous solution sequentially, and the solvent was evaporated under reduced pressure. 2.4 mL of tetrahydrofuran, 0.6 mL of water, 0.44 mL of acetic acid, 0.42 g sodium formate and 50 mg of 3.9% palladium-carbon (ethylenediamine complex) were added to the obtained residue and stirred at 50° C. for 12 hours. After the reaction mixture was cooled to room temperature, ethyl acetate and 10% citric acid aqueous solution were added. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with 10% citric acid aqueous solution and a saturated sodium chloride aqueous solution sequentially, and the solvent was evaporated under reduced pressure. 10 mL of trifluoroacetic acid was added to the obtained residue and stirred at room temperature for 1 hour. The solvent was evaporated under reduced pressure and the obtained residue was purified with reversed-phase silica gel column chromatography [eluent; 60-100% acetonitrile/0.1% trifluoroacetic acid aqueous solution] to obtain 8.6 mg of 2-(benzamido)-4-(2-(benzofuran-5-yl)ethyl)benzoic acid as white solid.

Provenance & Evidence