Hydrochloric Acid → HCID 131730405, compound

Participants

Reaction Conditions

Reaction Steps

Trans-methyl 2-(4-chloro-2-fluorophenyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (500 mg, 1.30 mmol) (from example 45, step 1) was dissolved in MeOH (6 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (0.381 mL, 1.30 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, 0.079 mL, 1.30 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 (6.67 mL, 40.05 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 crude trans-methyl 2-(4-chloro-2-fluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.45 g, 98%) as a slightly yellow dry film. MS m/z 355 (M+H)+

Provenance & Evidence