Under a nitrogen atmosphere, 2-{4-[(9R)-9-hydroxy-2-(3-hydroxy-3-methylbutyloxy)-9-(trifluoromethyl)-9H-fluoren-4-yl]-1H-pyrazol-1-yl}-2-methylpropionic acid (66.7 g) was dissolved in N,N-dimethylformamide (480 ml), 1-hydroxybenzotriazole (HOBt) 1 hydrate (27.6 g), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide (WSC) hydrochloride (34.6 g) and 28% aqueous ammonia (24.5 ml) were added, and the mixture was stirred at room temperature overnight. The reaction mixture was ice-cooled, water (630 ml) and 2N hydrochloric acid (330 ml) were added dropwise, and the mixture was extracted with ethyl acetate (800 ml). The obtained aqueous layer was extracted again with ethyl acetate (500 ml). The obtained organic layers were combined, and washed successively with water (500 ml, twice), saturated aqueous sodium hydrogen carbonate (500 ml), and saturated brine (500 ml). The obtained organic layer was dried over anhydrous sodium sulfate, the insoluble material was filtered off, and the solvent in the filtrate was evaporated to give the title compound (60.0 g).
