Hydrochloric Acid → HCID 68502101, compound

Participants

Reaction Conditions

Reaction Steps

Cis-methyl 2-(3,5-dichlorophenyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (3.57 g, 8.87 mmol) was dissolved in MeOH (36.4 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (2.335 mL, 8.87 mmol) in water (3.64 mL) was added and the mixture stirred at −40° C. for 20 min. Hydroxylamine (50% by weight in water, 0.544 mL, 8.87 mmol) was added and stirring continued at −40° C. for 3.5 h. The reaction mixture was then transferred to a preheated 80° C. solution of 6 M hydrogen chloride (45.9 mL, 275.11 mmol) and heating was continued for 20 min. The solvent was then evaporated. DCM and water 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 250×50 ID mm) using a gradient of 25-65% Acetonitrile in H2O/MeCN/AcOH 95/5/0.2 buffer over 30 minutes with a flow of 100 mL/min. Cis-methyl 2-(3,5-dichlorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (2.000 g, 60.7%) was isolated as a white solid. 1H NMR (400 MHz, cd3od) δ 1.82-1.93 (m, 1H), 2.13-2.27 (m, 2H), 2.30-2.39 (m, 1H), 3.06-3.16 (m, 1H), 3.42-3.53 (m, 1H), 3.66 (s, 3H), 4.04-4.12 (m, 1H), 5.06 (dd, 1H), 5.64 (d, 1H), 7.14-7.18 (m, 2H), 7.27 (t, 1H). MS m/z 371 (M+H)+

Provenance & Evidence