Hydrochloric Acid → HCID 68500267, compound

Participants

Reaction Steps

A solution of trans-methyl 2-benzyl-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (6.35 g, 18.3 mmol) in MeOH (2 mL) was added to a solution of NaOH (0.77 g, 19.4 mmol) in MeOH/H2O (15 mL/0.9 mL) at −30° C. After 10 minutes was added a solution of hydroxylamine hydrochloride (2.54 g, 36.6 mmol) and NaOH (1.46 g, 36.6 mmol) in MeOH (18 mL) and H2O (18 mL). Stirring was continued at −30° C. for 30 minutes. The reaction mixture was then poured into concentrated HCl (20 mL) held at 80° C. The solution was stirred for 30 minutes. The organic solvent was evaporated and the aqueous phase extracted with DEE (×3). The organic phase was dried over Na2SO4 and evaporated to give a solid, 3.68 g, which was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×20 ID mm) using a gradient of 20-70% acetonitrile in H2O/MeCN/FA 95/5/0.2 buffer, over 18 minutes with a flow of 19 mL/minutes. Trans-methyl-2-benzyl-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (2.54 g, 54.6%) was isolated as a solid. 1H NMR (600 MHz, cdcl3) δ 1.50-2.21 (m, 4H), 2.91 (m, 2H), 3.10 (m, 2H), 3.58 (d, 3H), 4.04-4.41 (m, 1H), 4.43-4.82 (m, 1H), 5.55-5.84 (m, 1H), 7.15-7.30 (m, 5H); MS m/z 317 (M+H)+.

Provenance & Evidence