反应详情

温度

50 °C

2-{4-[(9R)-9-Hydroxy-2-(3-hydroxy-3-methylbutyloxy)-9-(trifluoromethyl)-9H-fluoren-4-yl]-1H-pyrazol-1-yl}-2-methylpropanamide (compound (2)) (60.0 g) obtained in the previous step was dissolved in ethyl acetate (109 ml), water (2 ml) was added, and the mixture was heated to 50° C. To this mixture were successively added dropwise hexane (226 ml), and a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate 2:1, 150 ml), and the mixture was allowed to cool to room temperature and stirred overnight. The precipitated solid was collected by filtration, and washed with a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=2:1, 180 ml). The obtained solid was dried under reduced pressure at room temperature overnight to give the title compound (52.2 g, optical purity 98.6% e.e.). The optical purity was determined under the HPLC analysis condition 2. Retention time of (R) form 11.3 min, retention time of (S) form 13.9 min. Specific optical rotation [α]p+37.9° (c=1.01 MeOH 25° C.)

1. temperatureto cool to room temperature
2. filtrationThe precipitated solid was collected by filtration
3. washwashed with a mixed solvent of hexane and ethyl acetate (hexane:ethyl acetate=2:1, 180 ml)
4. customThe obtained solid was dried under reduced pressure at room temperature overnight