Hydrochloric Acid → HCID 68500601, compound

Participants

Reaction Conditions

Reaction Steps

Cis-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-phenylpiperidine-1-carboxylate (1.913 g, 5.74 mmol) was dissolved in MeOH (15 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (0.230 g, 5.74 mmol) dissolved in water (1.500 mL) was added during 5 min and the colourless solution continued to stir at −40° C. for 20 min. Hydroxylamine (50% by weight in water, 0.352 mL, 5.74 mmol) was added during 8 min. The resulting solution was stirred at −40° C. for 2 h 15 min. The mixture was then rapidly poured into a prewarmed (80° C.) solution of 6 M hydrogen chloride (24 mL, 144.00 mmol) and the mixture continued to stir at 80° C. for 20 min. The solvent was evaporated and MTBE/water added. The phases were separated and the organic phase evaporated to yield a slightly yellow oil. The compound was purified by preparative HPLC in 2 injections on a XBridge C18 column (10 μm 250×50 ID mm) using a gradient of 0-30% Acetonitrile in H2O/MeCN/NH3 95/5/0.2 buffer over 20 minutes with a flow of 100 mL/min. Cis-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-phenylpiperidine-1-carboxylate (1.344 g, 77%) was isolated as a white solid. 1H NMR (600 MHz, cdcl3) δ 1.77-1.85 (m, 1H), 2.10-2.18 (m, 1H), 2.19-2.28 (m, 1H), 2.32-2.39 (m, 1H), 3.01-3.08 (m, 1H), 3.37 (ddd, 1H), 3.64 (s, 3H), 4.15 (ddd, 1H), 5.08-5.13 (m, 1H), 5.48 (s, 1H), 7.13-7.20 (m, 3H), 7.27 (t, 2H). MS m/z 303 (M+H)+

Provenance & Evidence