反应详情

温度

-40 °C

Cis-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate (1.888 g, 4.87 mmol) was dissolved in MeOH (18 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (0.195 g, 4.87 mmol) dissolved in water (1.800 mL) was added during 10 min and the colourless solution continued to stir at −40° C. for 20 min. Hydroxylamine (50% by weight in water, 0.299 mL, 4.87 mmol) was added during 8 min. The resulting solution was stirred at −40° C. for 3 h 20 min. The mixture was then transferred into a prewarmed (80° C.) solution of 6 M hydrogen chloride (24 mL, 144.00 mmol) and the mixture continued to stir at 80° C. for 20 min. The solvent was evaporated and DCM/water added. The phases were separated and the organic phase passed through a phase separator and evaporated to yield a yellow oil. The compound was purified by preparative HPLC in 3 injections on a XBridge C18 column (10 μm 250×50 ID mm) using a gradient of 5-30% Acetonitrile in H2O/MeCN/NH3 95/5/0.2 buffer over 20 minutes with a flow of 100 mL/min. A mixture of cis-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate and trans-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)-piperidine-1-carboxylate (1.027 g, 59%) was obtained as white solid after freeze drying. MS m/z 357 (M+H)+

1. additionwas added during 10 min
2. stirringThe resulting solution was stirred at −40° C. for 3 h 20 min
3. stirringto stir at 80° C. for 20 min
4. customThe solvent was evaporated
5. additionDCM/water added
6. customThe phases were separated
7. customevaporated
8. customto yield a yellow oil
9. customThe compound was purified by preparative HPLC in 3 injections on a XBridge C18 column (10 μm 250×50 ID mm)
10. custombuffer over 20 minutes
11. additionA mixture of cis-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate