反应详情

To a mixture of 4-(cyclohexyl{2-ethyl-5-[4-(trifluoromethyl)phenyl]thiophen-3-yl}methoxy)benzoic acid (251 mg) synthesized above, ethyl β-alaninate hydrochloride (94.8 mg), 1-hydroxybenzotriazole monohydrate (94.5 mg), triethylamine (86.0 μL) and N,N-dimethylformamide (10 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (118 mg), and the mixture was stirred at room temperature for 3 hr. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane to ethyl acetate:hexane=2:3, volume ratio) to give a colorless oil. To a mixture of the obtained oil, tetrahydrofuran (5 mL) and ethanol (5 mL) was added 1N aqueous sodium hydroxide solution (2 mL), and the mixture was stirred at room temperature for 1 hr. 1N Hydrochloric acid (2.5 mL) was added to the reaction mixture, the organic solvent was evaporated under reduced pressure, and the mixture was extracted with ethyl acetate. The extract was washed with water and brine, dried over magnesium sulfate and concentrated under reduced pressure to give a white solid. The solid was recrystallized from ethyl acetate-hexane to give the title compound (117 mg, 40%) as a colorless crystal.

1. customto quench
2. customthe reaction
3. extractionthe mixture was extracted with ethyl acetate
4. washThe extract was washed with brine
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by silica gel column chromatography (hexane to ethyl acetate:hexane=2:3, volume ratio)
8. customto give a colorless oil
9. stirringthe mixture was stirred at room temperature for 1 hr
10. customthe organic solvent was evaporated under reduced pressure
11. extractionthe mixture was extracted with ethyl acetate
12. washThe extract was washed with water and brine
13. dry with materialdried over magnesium sulfate
14. concentrationconcentrated under reduced pressure
15. customto give a white solid
16. customThe solid was recrystallized from ethyl acetate-hexane