反应详情

To a solution of diethyl malonate (4.71 g) in tetrahydrofuran (40 ml) was gradually added sodium hydride (60%, oil, 1.07 g) at 0° C. The mixture was stirred for 10 min and a solution of 4-chloromethyl-5-(4-trifluoromethylphenyl)isoxazole (3.50 g) in tetrahydrofuran (40 ml) was added dropwise at 0° C. The mixture was stirred at room temperature for 15 hr. The reaction mixture was poured into water, acidified with 2N hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was dissolved in a mixture of 6N hydrochloric acid (40 ml) and acetic acid (60 ml) and heated under reflux for 8 hr. The reaction mixture was concentrated, and water was added to the residue. The obtained colorless crystals were filtrated, dried and recrystallized from ethyl acetate to give a colorless prism (3.00 g, yield 79%) of 3-[5-(4-trifluoromethylphenyl)-4-isoxazolyl]propionic acid. melting point: 171–172° C.

1. customat 0° C
2. stirringThe mixture was stirred at room temperature for 15 hr
3. extractionextracted with ethyl acetate
4. washThe ethyl acetate layer was washed with saturated brine
5. dry with materialdried (MgSO4)
6. concentrationconcentrated
7. dissolutionThe residue was dissolved in a mixture of 6N hydrochloric acid (40 ml) and acetic acid (60 ml)
8. temperatureheated
9. temperatureunder reflux for 8 hr
10. concentrationThe reaction mixture was concentrated
11. additionwater was added to the residue
12. filtrationThe obtained colorless crystals were filtrated
13. customdried
14. customrecrystallized from ethyl acetate