Hydrochloric Acid → HCID 131730432, compound

Participants

Reaction Conditions

Reaction Steps

Trans-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(2-fluoro-4-(trifluoromethyl)phenyl)piperidine-1-carboxylate (430 mg, 1.03 mmol) (from example 73, step 1) was dissolved in MeOH (3 mL) and cooled to −45° C. under nitrogen. Sodium hydroxide (0.302 mL, 1.03 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, 0.063 mL, 1.03 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 (5.28 mL, 31.68 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 oil. Crude trans-methyl 2-(2-fluoro-4-(trifluoromethyl)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (398 mg, quant.) was isolated. MS m/z 387 (M−H)−

Provenance & Evidence