Hydrochloric Acid → HCID 66732768, compound

Participants

Reaction Conditions

Reaction Steps

Cis-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(4-(trifluoromethoxy)benzyl)piperidine-1-carboxylate (2.475 g, 5.74 mmol) was dissolved in MeOH (20 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (1.687 mL, 5.74 mmol) dissolved in water (2.000 mL) was added during 10 min and the yellow solution continued to stir at −40° C. for 20 min. Hydroxylamine (50% by weight in water, 0.352 mL, 5.74 mmol) was added during 8 min. The resulting solution was stirred at −40° C. for 3 h. The mixture was then rapidly poured into a prewarmed (80° C.) solution of 6 M hydrogen chloride (29.5 mL, 177.28 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 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(4-(trifluoromethoxy)benzyl)piperidine-1-carboxylate (1.41 g, 61.4%) was isolated. MS m/z 401 (M+H)+

Provenance & Evidence