Hydrochloric Acid → HCID 66731837, compound

Participants

Reaction Conditions

Reaction Steps

Methyl 2-(2-chloro-4-fluorophenyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (1.655 g, 4.29 mmol) was dissolved in MeOH (22 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (0.180 g, 4.50 mmol) dissolved in water (2.200 mL) was added and the mixture was stirred at −40° C. for 15 min. Hydroxylamine (50% by weight in water, 0.276 mL, 4.50 mmol) was added. The resulting solution was stirred at −40° C. for 1 h. The mixture was then transferred with a pipette into a prewarmed (80° C.) solution of 6 M hydrogen chloride (22.16 mL, 132.98 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. The compound was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×50 ID mm) using a gradient of 15-55% Acetonitrile in H2O/MeCN/FA 95/5/0.2 buffer over 25 minutes with a flow of 100 mL/min (3 runs). Methyl 2-(2-chloro-4-fluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.995 g, 65.4%) was yielded as a white solid. MS m/z 355 (M+H)+

Provenance & Evidence