反应详情

温度

-40 °C

Trans-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(4-(trifluoromethyl)phenyl)piperidine-1-carboxylate (0.467 g, 1.16 mmol) (from example 33, step 1) was dissolved in MeOH (4 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (0.047 g, 1.16 mmol) dissolved in water (0.4 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, 0.071 mL, 1.16 mmol) was added during 8 min. The resulting solution was stirred at −40° C. for 3.5 h. The mixture was then transferred into a prewarmed (80° C.) solution of 6 M hydrogen chloride (6 mL, 36.00 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 crude trans-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(4-(trifluoromethyl)phenyl)piperidine-1-carboxylate (0.432 g, quant.) as a yellow oil. MS m/z 371 (M+H)+

1. additionwas added during 10 min
2. stirringThe resulting solution was stirred at −40° C. for 3.5 h
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