Hydrochloric Acid → HCID 131730478, compound

Participants

Reaction Conditions

Reaction Steps

A solution of methyl 2-(4-chlorobenzyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (780 mg, 2.04 mmol) (from example 115, step 2) in MeOH (5 mL) was added to a solution of sodium hydroxide (1.705 mL, 2.05 mmol) in MeOH/H2O (1.608 mL/0.097 mL) at −30° C. After 10 min a solution of hydroxylamine hydrochloride (284 mg, 4.09 mmol) and sodium hydroxide (163 mg, 4.09 mmol) in MeOH (5 mL) and H2O (5 mL) was added. Stirring was continued at −30° C. for 30 min. The reaction solution was poured into 6 M HCl (3.40 mL, 20.43 mmol) at 80° C. and heated at 80° C. for 30 min. Concentration of the organic solvent and extraction with diethyl ether (×3), drying over Na2SO4 and evaporation gave a yellow foam. Purification using prepLC (pH=3, large column 20-80% MeCN over 30 min) yielded trans-methyl 2-(4-chlorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (272.5 mg, 38%). 1H NMR (400 MHz, cdcl3) δ 1.44-2.18 (m, 4H), 2.70-3.01 (m, 2H), 3.02-3.14 (m, 2H), 3.42-3.76 (m, 3H), 4.04-4.37 (m, 1H), 4.39-4.79 (m, 1H), 5.64 (s, 1H), 7.05-7.31 (m, 4H). MS m/z 351, 353 (M+H)+

Provenance & Evidence