Sodium Hydroxide → Fasiglifam

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl [(3S)-6-hydroxy-2,3-dihydro-1-benzofuran-3-yl]acetate (10.0 g) and 3′-chloromethyl-2,6-dimethyl-4-[3-(methylsulfonyl)propoxy]biphenyl (17.6 g) in N,N-dimethylformamide (30.0 mL) was added tripotassium phosphate (16.8 g), and the mixture was stirred at 60° C. for 3 hr. 2.4M Aqueous sodium hydroxide solution (32.9 g) was added, and the mixture was stirred at 80° C. for 2 hr. The reaction mixture was cooled, water (100 mL) was added, and the mixture was extracted with toluene (50 mL). To the aqueous layer was added toluene (50 mL), and the mixture was extracted. To the obtained aqueous layer were added acetone (10 mL) and concentrated hydrochloric acid (17.6 mL), and the mixture was stirred at 30° C. for 1 hr, at 50° C. for 30 min, and at 25° C. for 2 hr. The precipitated crystals were collected by filtration, and washed with a mixed solution (50 mL) of acetone.water (3:7) and then water (50 mL). The obtained crystals were dried at 60° C. under reduced pressure to give [(3S)-6-({2′,6′-dimethyl-4′-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetic acid (24.3 g). 100% ee. (high performance liquid chromatography conditions)

Provenance & Evidence