反应详情

A 250-mL round-bottom flask was purged with nitrogen and a suspension of LiAlH4 (2.5 g, 65.8 mmol, 2.87 equiv) in tetrahydrofuran (50 mL) was added. This was followed by the addition of a solution of methyl 5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazole-4-carboxylate (7.5 g, 22.9 mmol, 1.00 equiv) in tetrahydrofuran (50 mL) dropwise at −10°C. The resulting reaction mixture was stirred fo(30 min at −10°C. When the reaction was complete, it was quenched by the addition of 3 mL of ethyl acetate, followed by 3 mL of water and O1 mL of 15% aqueous NaOH, all whilst maintaining a vigorous stirring. The resulting white precipitate was filtered through celite®, and the filter cake was washed with 200 mL of ethyl acetate. The filtrate was washed with brine (2×100 mL), dried over anhydrous sodium sulfate, and concentrated under vacuum. This resulted in 7 g of (5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methanol as yellow oil. (1H-NM(300 MHz, CDCl3) δ 7.56 (m, 2H), 7.41 (m, 2H), 4.50 (s, 2H), 2.20 (m, 1H), 1.72 (s, 1H, —OH) 1.11-1.28 (m, 4H).

1. customA 250-mL round-bottom flask was purged with nitrogen
2. additionwas added
3. customThe resulting reaction mixture
4. custom30 min
5. customat −10°C
6. customit was quenched by the addition of 3 mL of ethyl acetate
7. temperatureO1 mL of 15% aqueous NaOH, all whilst maintaining a vigorous stirring
8. filtrationThe resulting white precipitate was filtered through celite®
9. washthe filter cake was washed with 200 mL of ethyl acetate
10. washThe filtrate was washed with brine (2×100 mL)
11. dry with materialdried over anhydrous sodium sulfate
12. concentrationconcentrated under vacuum
13. customThis resulted in 7 g of (5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methanol as yellow oil