Hydrochloric Acid → HCID 68502462, compound

Participants

Reaction Steps

A solution of methyl 2-(cyclohexylmethyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (1.5 g, 4.2 mmol) in MeOH (4 mL) was added to a solution of NaOH (221 mg, 5.5 mmol) in MeOH/H2O (4 mL/0.25 mL) at −30° C. After 10 minutes was added hydroxylamine-HCl (0.59 g, 8.5 mmol) and NaOH (0.339 g, 8.5 mmol) in MeOH (5 mL) and H2O (5 mL). Stirring was continued at −30° C. for 30 minutes. The reaction solution was poured into 6M HCl (6 mL) at 80° C. and heated for 30 minutes. The reaction mixture was partitioned between water and ethyl acetate. The organic phase was isolated, dried with Na2SO4, filtered through Celite® and the solvent was evaporated. Crude 1.7 g. Purification using reversed phase chromatography, which gave 0.3 g, yield 22%. Chiral separation using Chiralcel OJ, mobile phase heptane/ethanol 80/20 at 40° C. gave of (2R,4S)-methyl 2-(cyclohexylmethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.11 g). 1H NMR (600 MHz, cdcl3) δ 0.91 (d, 2H), 1.06-1.39 (m, 5H), 1.68 (dt, 7H), 1.85 (s, 2H), 1.94 (s, 1H), 2.99 (t, 2H), 3.68 (s, 3H), 4.11 (d, 1H), 4.50 (d, 1H), 5.60 (s, 1H). [α]20D +3.2 (MeCN, c=1).

Provenance & Evidence