反应详情

温度

-40 °C

Trans-methyl 2-(cyclohexyloxymethyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (210 mg, 0.57 mmol) (from example 84, step 1) was dissolved in MeOH (3 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (23.87 mg, 0.60 mmol) dissolved in water (0.300 mL) was added and the mixture was stirred at −40° C. for 15 min. Hydroxylamine (50% by weight in water, 0.037 mL, 0.60 mmol) was added. The resulting solution was stirred at −40° C. for 1 h. The mixture was transferred into a prewarmed (80° C.) solution of 6 M hydrogen chloride (2.94 mL, 17.62 mmol) and the mixture was stirred at 80° C. for 20 min. Water and DCM were added and the phases separated. The aqueous phase was extracted with DCM and the combined organic layers were filtered through a phase separator and evaporated. The compound was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×50 ID mm) using a gradient of 15-55% Acetonitrile in H2O/MeCN/AcOH 95/5/0.2 buffer over 20 minutes with a flow of 100 mL/min. Trans-methyl 2-(cyclohexyloxymethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (121 mg, 63%) was isolated. MS m/z 339 (M+H)+

1. additionwas added
2. stirringThe resulting solution was stirred at −40° C. for 1 h
3. stirringthe mixture was stirred at 80° C. for 20 min
4. customthe phases separated
5. extractionThe aqueous phase was extracted with DCM
6. filtrationthe combined organic layers were filtered through a phase separator
7. customevaporated
8. customThe compound was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×50 ID mm)
9. custombuffer over 20 minutes