反应详情

A solution of trans-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(4-(trifluoromethyl)benzyl)-piperidine-1-carboxylate (0.4 g, 0.96 mmol) in methanol (3 mL) was added dropwise to a solution of NaOH (0.042 g, 1.06 mmol) in methanol/water (3 mL/0.2 mL) at −30° C. After stirring for 10 min a solution of hydroxylamine hydrochloride (0.134 g, 1.93 mmol) and NaOH (0.077 g, 1.93 mmol) in methanol/water (5 mL/5 mL) was added at −30° C. Stirring was continued for 30 min at −30° C. The solution was added dropwise to 6 M HCl at 80° C. Stirred 30 min at 80° C. The reaction mixture was dissolved between water and ethyl acetate. The organic phase was isolated, dried with Na2SO4, filtered through celite and the solvent was evaporated. Acidic reversed phase chromatography, gradient 35% to 75% acetonitrile. Trans-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(4-(trifluoromethyl)benzyl)piperidine-1-carboxylate (205 mg, 55.4%) was isolated. 1H NMR (600 MHz, cdcl3) δ 1.63 (d, 2H), 1.98 (d, 2H), 2.81-3.14 (m, 4H), 3.55 (d, 3H), 4.21 (d, 1H), 4.63 (d, 1H), 5.63 (s, 1H), 7.22-7.37 (m, 2H), 7.54 (d, 2H). MS m/z 385 (M+H)+

1. additionwas added at −30° C
2. stirringStirred 30 min at 80° C
3. customThe organic phase was isolated
4. dry with materialdried with Na2SO4
5. filtrationfiltered through celite
6. customthe solvent was evaporated