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

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl (6-hydroxy-1-benzofuran-3-yl)acetate (17.7 g) and 3′-(chloromethyl)-2,6-dimethyl-4-[3-(methylsulfonyl)propoxy]biphenyl (31.5 g) in N,N-dimethylformamide (60 mL) was added tripotassium phosphate (27.4 g), and the mixture was stirred at 70° C. for 3 hr. The mixture was allowed to cool to room temperature, toluene (240 mL) and water (240 mL) were added, and an extraction operation was performed. The aqueous phase was extracted with toluene (240 mL), and the extract was washed with water (240 mL) and saturated brine (240 mL), and concentrated. The obtained solid was dissolved in dimethyl sulfoxide (100 mL), and 2N sodium hydroxide (47.2 mL) was added at room temperature. After stirring at 70° C. for 1 hr and at 25° C. for 20 hr, the aqueous layer was acidified with 6N hydrochloric acid to pH 1-2, water (240 mL) and ethyl acetate (240 mL) were added, and an extraction operation was performed. The aqueous layer was extracted with ethyl acetate (200 mL), and the combined organic layer was washed with water (240 mL) and concentrated. The crude product was recrystallized from acetone (120 mL)-water (240 mL), and the obtained solid was dried at 60° C. under reduced pressure to give the title compound (34.1 g) as white crystals.

Provenance & Evidence