4-Fluoro-1-naphthoic acid → 4-Fluoro-N-[1-(4-fluorophenyl)-1-hydroxy-3-(2,2,3,3-tetrafluoro-1,4-benzodioxin-6-yl)propan-2-yl]naphthalene-1-carboxamide

Participants

Reaction Steps

To a solution of (1RS,2SR)-2-amino-1-(4-fluorophenyl)-3-(2,2,3,3-tetrafluoro-2,3-dihydro-1,4-benzodioxin-6-yl)propan-1-ol (250 mg, 0.67 mmol) in acetonitrile (20 ml) were added 4-fluoronaphthalenecarboxylic acid (127 mg, 0.67 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (191 mg, 1.00 mmol) and 1-hydroxybenzotriazole-hydrate (102 mg, 0.67 mmol), and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (100 ml) and extracted with ethyl acetate (100 ml×2). The extract was washed successively with water and saturated brine, dried (anhydrous magnesium sulfate) and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate). Recrystallization from ethyl acetate-hexane gave the objective substance (290 mg, 80%).

Provenance & Evidence