反应详情

温度

100 °C

To a solution of an optically active form (27.9 g) of 2-[4-(2-fluoro-9-hydroxy-9-trifluoromethyl-9H-fluoren-4-yl)-pyrazol-1-yl]-propionic acid ethyl ester and paraformaldehyde (17.0 g) in dimethylformamide (100 ml) was added at room temperature a 1M solution (170 ml) of tetrabutylammonium fluoride in tetrahydrofuran, and the mixture was stirred at 100° C. for 6 hr. The reaction mixture was filtered through celite, and the solid was washed with ethyl acetate (100 ml). To the filtrate was added 1N hydrochloric acid (400 ml), and the mixture was extracted with ethyl acetate (100 ml). The separated aqueous layer was extracted twice with ethyl acetate (100 ml). The combined organic layer was successively washed once with 1N hydrochloric acid (100 ml), twice with brine (water/saturated brine=100 ml/10 ml) and once with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was azeotroped twice with toluene to give the title compound (26.6 g).

1. filtrationThe reaction mixture was filtered through celite
2. washthe solid was washed with ethyl acetate (100 ml)
3. additionTo the filtrate was added 1N hydrochloric acid (400 ml)
4. extractionthe mixture was extracted with ethyl acetate (100 ml)
5. extractionThe separated aqueous layer was extracted twice with ethyl acetate (100 ml)
6. washThe combined organic layer was successively washed once with 1N hydrochloric acid (100 ml), twice with brine (water/saturated brine=100 ml/10 ml) and once with saturated brine
7. dry with materialdried over anhydrous sodium sulfate
8. concentrationconcentrated under reduced pressure
9. customThe obtained residue was azeotroped twice with toluene