Hydrochloric Acid → HCID 131730423, compound

Participants

Reaction Conditions

Reaction Steps

Trans-methyl 2-(4-chloro-3,5-difluorophenyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (178 mg, 0.44 mmol) (from example 65, step 1) was dissolved in MeOH (2 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (18.51 mg, 0.46 mmol) dissolved in water (0.200 mL) was added and the mixture was stirred at −40° C. for 15 min. Hydroxylamine (50% by weight in water, 0.028 mL, 0.46 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 (2.278 mL, 13.67 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. Crude trans-methyl 2-(4-chloro-3,5-difluorophenyl)-4-(3-oxo-2,3-dihydro-isoxazol-5-yl)piperidine-1-carboxylate (158 mg, 96%) was isolated as a light yellow oil. MS m/z 273 (M+H)+

Provenance & Evidence