Cesium carbonate → [6-({2',6'-Dimethyl-4'-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-1-benzofuran-3-yl]acetic acid

Participants

Reaction Steps

A solution of tris(dibenzylideneacetone)dipalladium (0). dibenzylideneacetone solvate (42.5 mg) and 2-(dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl) (76.18 mg) in toluene (4 ml) and 1,2-dimethoxyethane (4 ml) was stirred at 70° C. for 1 hr. After allowing to cool to room temperature, methyl(S)-2-(6-(((trifluoromethyl)sulfonyl)oxy)-2,3-dihydrobenzofuran-3-yl)acetate (864.3 mg), (2′,6′-dimethyl-4′-(3-(methylsulfonyl)propoxy)-[1,1′-biphenyl]-3-yl)methanol (1.15 g) and cesium carbonate (2.60 g) were added, and the mixture was stirred at 85° C. for 6 hr. The mixture was allowed to cool to room temperature and concentrated, toluene (30 mL) and water (30 mL) were added, and an extraction operation was performed. The organic layer was washed with water (30 mL) and 10% brine (30 mL), and concentrated. The obtained oil was dissolved in dimethyl sulfoxide (15 mL), and 2N sodium hydroxide (4 mL) was added at room temperature. The mixture was stirred at 70° C. for 1 hr, and allowed to cool to room temperature. Ethyl acetate (30 mL) and water (30 mL) were added, and the mixture was partitioned. The aqueous layer was acidified with 6N hydrochloric acid to pH 1, ethyl acetate (30 mL) was added, and an extraction operation was performed. The organic layer was washed with water (30 mL), and concentrated. The crude product was recrystallized from acetone (15 mL)-water (30 mL), and the obtained solid was dried at 60° C. under reduced pressure to give the title compound (706 mg) as white crystals. Yield 53%.

Provenance & Evidence