Hydrochloric Acid → HCID 66732055, compound

Participants

Reaction Conditions

Reaction Steps

Cis-methyl 2-(4-chloro-2-fluorophenyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (2.31 g, 5.99 mmol) was dissolved in MeOH (24 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (1.761 mL, 5.99 mmol) was added during 10 min and the yellow solution continued to stir at −40° C. for 20 min. Hydroxylamine (50% by weight in water, 0.367 mL, 5.99 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 (30.8 mL, 185.01 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 slightly yellow solid. The compound was purified by preparative HPLC on a XBridge C18 column (10 μm 250×50 ID mm) using a gradient of 10-55% Acetonitrile in H2O/MeCN/NH3 95/5/0.2 buffer over 30 minutes with a flow of 100 mL/min. Cis-methyl 2-(4-chloro-2-fluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (1 g, 47%) was isolated after. MS m/z 355 (M+H)+

Provenance & Evidence