反应详情

To a solution of ethyl 5-phenyl-4-(trifluoromethyl)isoxazole-3-carboxylate (Intermediate I-5C, 3.6 g, 12.6 mmol) in methanol (100 mL) and water (20 mL) at room temperature was added lithium hydroxide, monohydrate (0.583 g, 13.9 mmol). The reaction mixture was stirred at room temperature for 30 minutes. The methanol was removed under reduced pressure, and the residue was diluted with water (˜100 mL). Ethyl ether (200 mL) was added, and the pH of the aqueous layer was adjusted to <1 with a 1N aqueous solution of hydrochloric acid. The mixture was transferred to a separatory funnel, and after agitation, the layers were separated. The organic layer was washed with brine (100 mL), dried over anhydrous magnesium sulfate, and concentrated to afford 5-phenyl-4-(trifluoromethyl)isoxazole-3-carboxylic acid (3.12 g, 12.13 mmol, 96% yield) as a white, crystalline solid. The compound had an HPLC retention time=2.58 minutes (condition B); MS:(M+Na)=279.95; 1H NMR (400 MHz, CDCl3) δ ppm 7.53-7.64 (m, 3H), and 7.70 (d, J=7.5 Hz, 2H).

1. customThe methanol was removed under reduced pressure
2. additionthe residue was diluted with water (˜100 mL)
3. additionEthyl ether (200 mL) was added
4. customThe mixture was transferred to a separatory funnel
5. customafter agitation, the layers were separated
6. washThe organic layer was washed with brine (100 mL)
7. dry with materialdried over anhydrous magnesium sulfate
8. concentrationconcentrated