Hydrochloric Acid → HCID 68501730, compound

Participants

Reaction Conditions

Reaction Steps

A solution of cis-methyl 2-(4-chlorobenzyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (1.45 g, 3.80 mmol) in MeOH (10 mL) was added to a solution of sodium hydroxide (3.16 mL, 3.80 mmol) in MeOH/H2O (2.981 mL/0.179 mL) at −30° C. After 10 min a solution of hydroxylamine hydrochloride (0.528 g, 7.59 mmol) and sodium hydroxide (0.304 g, 7.59 mmol) in MeOH (10 mL) and H2O (10 mL) was added. Stirring was continued at −30° C. for 30 min. The reaction solution was poured into 6 M HCl (6.33 mL, 37.97 mmol) at 80° C. and heated at 80° C. for 1 hour. Concentration of the organic solvent and extraction with diethyl ether (×3), drying over Na2SO4 and evaporation gave a yellow foam. Purification using prepLC (2 injections, pH=3, large column 20-80% MeCN over 30 min) yielded cis-methyl 2-(4-chlorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (557 mg, 41%). 1H NMR (400 MHz, cdcl3) δ 1.83-2.00 (m, 3H), 2.02-2.12 (m, 1H), 2.59 (dd, 1H), 2.77 (dd, 1H), 2.97-3.02 (m, 1H), 3.08-3.20 (m, 1H), 3.62 (s, 3H), 4.00 (dd, 1H), 4.21-4.29 (m, 1H), 5.73 (s, 1H), 7.04 (d, 2H), 7.21-7.25 (m, 2H). MS m/z 351, 353 (M+H)+

Provenance & Evidence