Hydrochloric Acid → HCID 131730397, compound

Participants

Reaction Conditions

Reaction Steps

Trans-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(4-(methylsulfonyl)phenyl)piperidine-1-carboxylate (505 mg, 1.23 mmol) (from example 38, step 1) was suspended in MeOH (5 mL) and cooled to −40° C. 3.8 M sodium hydroxide (0.323 mL, 1.23 mmol) in water was added. After 20 min, hydroxylamine (50% in water, 0.075 mL, 1.23 mmol) was added and stirring continued at −40° C. for 3 h. The reaction mixture was then added to a prewarmed 80° C. solution of 6 M hydrogen chloride (6.14 mL, 36.82 mmol) and stirred for 20 min. The solvent was evaporated in vacuo. DCM (50 mL) and water (50 mL) were added, shaken and the phases separated. The organic phase was dried with a phase separator and evaporated in vacuo. The residue was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×20 ID mm) using a gradient of 15-40% Acetonitrile in H2O/MeCN/AcOH 95/5/0.2 buffer, over 25 minutes with a flow of 19 mL/min. Trans-methyl 2-(4-(methylsulfonyl)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (301 mg, 64.5%) was isolated. 1H NMR (600 MHz, cdcl3) δ 1.61-1.73 (m, 1H), 1.91-1.99 (m, 1H), 2.05-2.14 (m, 1H), 2.66-2.82 (m, 2H), 2.91 (t, 1H), 3.05 (s, 3H), 3.77 (s, 3H), 4.12-4.46 (m, 1H), 5.60-5.80 (m, 2H), 7.44 (d, 2H), 7.95 (d, 2H). MS m/z 381 (M+H)+

Provenance & Evidence