Hydrochloric Acid → HCID 131730409, compound

Participants

Reaction Conditions

Reaction Steps

Trans-methyl 2-(4-chloro-3-fluorophenyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (171 mg, 0.44 mmol) (from example 49, step 1) was dissolved in MeOH (2 mL) and cooled to −40° C. Sodium hydroxide (0.117 mL, 0.44 mmol) dissolved in water (0.200 mL) was added dropwise and the solution stirred for 20 min. Hydroxylamine (50% by weight in water, 0.024 mL, 0.44 mmol) was then added and stirring was continued for 3.5 h. The mixture was then transferred to a prewarmed 80° C. solution of 6 M hydrogen chloride (2.290 mL, 13.74 mmol) and stirring was continued at 80° C. for 20 min. The solvent was evaporated in vacuo and DCM (50 mL) and water (50 mL) were added. The phases were shaken, separated and the organic phase dried with a phase separator and evaporated in vacuo. The compound was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×20 ID mm) using a gradient of 10-60% Acetonitrile in H2O/MeCN/AcOH 95/5/0.2 buffer over 30 minutes with a flow of 19 mL/min. (2S,4S)-Methyl 2-(4-chloro-3-fluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (49.0 mg, 31.2%) was isolated as a white solid. 1H NMR (600 MHz, cdcl3) δ 1.58-1.70 (m, 1H), 1.85-2.06 (m, 2H), 2.60 (d, 1H), 2.73-2.96 (m, 2H), 3.73 (s, 3H), 4.04-4.44 (m, 1H), 5.42-5.78 (m, 2H), 6.92-7.05 (m, 2H), 7.38 (t, 1H). MS m/z 355 (M+H)+

Provenance & Evidence