Hydrochloric Acid → HCID 68501980, compound

Participants

Reaction Conditions

Reaction Steps

Cis-methyl 2-(3,5-di-tert-butylbenzyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (2.03 g, 4.42 mmol) was dissolved in MeOH (16 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (0.177 g, 4.42 mmol) dissolved in water (1.600 mL) was added during 10 min and the colourless solution continued to stir at −40° C. for 20 min. Hydroxylamine (50% by weight in water, 0.271 mL, 4.42 mmol) was added during 8 min. The resulting solution was stirred at −40° C. for 3.5 h. The mixture was then transferred into a prewarmed (80° C.) solution of 6 M hydrogen chloride (20 mL, 120.00 mmol) and the mixture continued to stir at 80° C. for 20 min. DCM and water were added. The phases were separated and the organic phase passed through a phase separator and evaporated to yield a yellow semi-solid. The compound was purified by preparative HPLC in 3 injections on a XBridge C18 column (10 μm 250×50 ID mm) using a gradient of 10-50% Acetonitrile in H2O/MeCN/NH3 95/5/0.2 buffer over 20 minutes with a flow of 100 mL/min. Cis-methyl 2-(3,5-di-tert-butylbenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (1.358 g, 72%) was isolated as a white solid. 1H NMR (600 MHz, cdcl3) δ 1.22-1.33 (m, 18H), 1.80-2.10 (m, 4H), 2.59-2.67 (m, 1H), 2.71-2.78 (m, 1H), 2.92-2.98 (m, 1H), 3.07-3.15 (m, 1H), 3.55 (s, 3H), 3.97 (dd, 1H), 4.18-4.27 (m, 1H), 5.68 (s, 1H), 6.92 (d, 2H), 7.22 (s, 1H). MS m/z 429 (M+H)+

Provenance & Evidence