反应详情

温度

-40 °C

Trans-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(3,4,5-trifluorophenyl)piperidine-1-carboxylate (59 mg, 0.15 mmol) (from example 60, step 1) was dissolved in MeOH (1 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (0.045 mL, 0.15 mmol) was added during 10 min and the yellow solution continued to stir at −40° C. for 20 min. Hydroxylamine (50% by weight in water, 9.33 μL, 0.15 mmol) was added during 8 min. The resulting solution was stirred at −40° C. for 3 h 15 min. The mixture was then rapidly poured into a prewarmed (80° C.) solution of 6 M hydrogen chloride (0.784 mL, 4.71 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, the organic phase passed through a phase separator and evaporated to yield crude trans-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3,4,5-trifluorophenyl)piperidine-1-carboxylate (53 mg, quant.) as a slightly yellow oil. MS m/z 357 (M+H)+

1. stirringThe resulting solution was stirred at −40° C. for 3 h 15 min
2. stirringto stir at 80° C. for 20 min
3. customThe solvent was evaporated
4. additionDCM/water added
5. customThe phases were separated
6. customevaporated