Hydrochloric Acid → HCID 131730501, compound

Participants

Reaction Conditions

Reaction Steps

Trans-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(3,4,5-trifluorobenzyl)piperidine-1-carboxylate (309 mg, 0.77 mmol) (from example 143, step 1) was dissolved in MeOH (5 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (0.203 mL, 0.77 mmol) in water (0.500 mL) was added and the mixture was stirred at −40° C. for 20 min. Hydroxylamine (50% in water, 0.047 mL, 0.77 mmol) was added and stirring continued at −40° C. for 3 h. The reaction mixture was then transferred to a preheated 80° C. solution of 6 M hydrogen chloride (3.98 mL, 23.87 mmol) and heating was continued for 20 min. The solvent was then evaporated. DCM (50 mL) and water (50 mL) were added, shaken and the phases separated. The organic phase was dried with a phase separator and evaporated in vacuo. The compound was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×20 ID mm) using a gradient of 10-55% Acetonitrile in H2O/MeCN/AcOH 95/5/0.2 buffer, over 30 minutes with a flow of 19 mL/min. Trans-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3,4,5-trifluorobenzyl)-piperidine-1-carboxylate (111 mg, 38.9%) was isolated. MS m/z 371 (M+H)+

Provenance & Evidence