Hydrochloric Acid → HCID 131730415, compound

Participants

Reaction Conditions

Reaction Steps

Trans-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(2-fluoro-4-(trifluoromethoxy)phenyl)-piperidine-1-carboxylate (420 mg, 0.96 mmol) (from example 58, step 1) was dissolved in MeOH (4 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (40.5 mg, 1.01 mmol) dissolved in water (0.400 mL) was added and the mixture was stirred at −40° C. for 15 min. Hydroxylamine (50% by weight in water, 62 μL, 1.01 mmol) was added. The resulting solution was stirred at −40° C. for 1 h. The mixture was then transferred into a prewarmed (80° C.) solution of 6 M hydrogen chloride (4.98 mL, 29.91 mmol) and the mixture was stirred at 80° C. for 15 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. Crude trans-methyl 2-(2-fluoro-4-(trifluoromethoxy)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (365 mg, 94%) was yielded as a colorless oil. MS m/z 405 (M+H)+

Provenance & Evidence