反应详情

温度

-30 °C

Methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(4-(methylsulfonyl)benzyl)piperidine-1-carboxylate (3.99 g, 9.38 mmol) was dissolved in MeOH (70 mL) and cooled to −30° C. NaOH (0.375 g, 9.38 mmol) dissolved in water (7 mL) was added during 10 min and the resulting colourless solution continued to stir at −30° C. for 20 min. Hydroxylamine (50% by weight in water, 0.575 mL, 9.38 mmol) was added dropwise. The resulting solution was stirred at −30° C. for 30 min. The mixture was then transferred into a prewarmed (80° C.) solution of 6 M HCl (30 mL, 180 mmol) and the mixture continued to stir at 80° C. for 20 min. The mixture was dissolved between ethyl acetate and water. The aqueous layer was extracted three more times with ethyl acetate. The combined organic layers were dried over Na2SO4, filtered through celite and the solvent was evaporated. The residue was purified using reversed phase chromatography, gradient acid buffer and acetonitril, started 35% and ended 40%. Methyl 2-(4-(methylsulfonyl)benzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (1.05 g, 28.4%) was isolated.

1. additionwas added during 10 min
2. stirringThe resulting solution was stirred at −30° C. for 30 min
3. stirringto stir at 80° C. for 20 min
4. extractionThe aqueous layer was extracted three more times with ethyl acetate
5. dry with materialThe combined organic layers were dried over Na2SO4
6. filtrationfiltered through celite
7. customthe solvent was evaporated
8. customThe residue was purified