Hydrochloric Acid → HCID 66741776, compound

Participants

Reaction Conditions

Reaction Steps

Cis-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(4-(methylsulfonyl)phenyl)piperidine-1-carboxylate (2.6 g, 6.32 mmol) was suspended in MeOH (100 mL). DCM (40 mL) was added and the reaction cooled to −40° C. 3.8 M sodium hydroxide (1.663 mL, 6.32 mmol) in water (10.00 mL) was added and the reaction stirred at −40° C. for 20 min. Hydroxylamine (50% in water, 0.387 mL, 6.32 mmol) was added and the reaction stirred at −40° C. for 3 h. The reaction mixture was then added to a prewarmed 80° C. solution of 6 M hydrogen chloride (63.2 mL, 379.13 mmol) and the reaction stirred for 30 min. The solvent was evaporated in vacuo. DCM (250 mL) and water (250 mL) 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 15-45% Acetonitrile in H2O/MeCN/AcOH 95/5/0.2 buffer over 30 minutes with a flow of 100 mL/min. Cis-methyl 2-(4-(methylsulfonyl)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (1.200 g, 49.9%) was isolated as a white solid. 1H NMR (600 MHz, cdcl3) δ 1.85-1.91 (m, 1H), 2.18-2.29 (m, 2H), 2.35-2.41 (m, 1H), 2.98 (s, 3H), 3.00-3.13 (m, 1H), 3.38-3.44 (m, 1H), 3.67 (s, 3H), 4.13-4.19 (m, 1H), 5.20 (t, 1H), 5.47 (s, 1H), 7.34 (d, 2H), 7.83 (d, 2H). MS m/z 381 (M+H)+

Provenance & Evidence