Hydrochloric Acid → HCID 68503711, compound

Participants

Reaction Conditions

Reaction Steps

Cis-methyl 2-(2,4-difluorophenyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (870 mg, 2.36 mmol) was dissolved in MeOH (9 mL) and cooled to −45° C. under nitrogen. Sodium hydroxide (0.693 mL, 2.36 mmol) was added during 10 min and the yellow solution continued to stir at −45° C. for 20 min. Hydroxylamine (50% by weight in water, 0.144 mL, 2.36 mmol) was added during 8 min. The resulting solution was stirred at −45° C. for 3 h. The mixture was then rapidly poured into a prewarmed (80° C.) solution of 6 M hydrogen chloride (12.13 mL, 72.78 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 a white solid. The compound was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×50 ID mm) using a gradient of 10-60% Acetonitrile in H2O/MeCN/AcOH 95/5/0.2 buffer over 30 minutes with a flow of 100 mL/min. Cis-methyl 2-(2,4-difluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (397 mg, 49%) was isolated. MS m/z 339 (M+H)+

Provenance & Evidence