Under a nitrogen atmosphere, 2-{4-[(9R)-9-hydroxy-2-(4-hydroxy-4-methylpentyloxy)-9-(trifluoromethyl)-9H-fluoren-4-yl]-1H-pyrazol-1-yl}-2-methylpropionic acid (89 mg) was dissolved in N,N-dimethylformamide (1 ml), ammonium chloride (28 mg), N,N-diisopropylethylamine (148 μl) and 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridin-1-ium 3-oxide hexafluorophosphate (HATU) (99 mg) were added, and the mixture was stirred at room temperature overnight. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate (twice). The obtained organic layer was washed successively with diluted brine (twice) and saturated brine. The obtained organic layer was dried over anhydrous magnesium sulfate, the insoluble material was filtered off, and the solvent in the filtrate was evaporated. The obtained residue was purified by silica gel thin layer chromatography (a mixture of chloroform and methanol at a mixing ratio 9:1 (chloroform:methanol) was used as an elution solvent) to give the title compound (48 mg, optical purity 96.9% e.e.). The optical purity was determined under the HPLC analysis condition 2. Retention time of (R) form 13.0 min, retention time of (S) form 14.4 min.
