Hydrochloric Acid → HCID 68507161, compound

Participants

Reaction Conditions

Reaction Steps

Cis-methyl 2-(4-chloro-3,5-difluorophenyl)-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (1.445 g, 3.58 mmol) was dissolved in MeOH (14 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (0.150 g, 3.76 mmol) dissolved in water (1.4 mL) was added and the mixture was stirred at −40° C. for 15 min. Hydroxylamine (50% by weight in water, 0.230 mL, 3.76 mmol) was added. The resulting solution was stirred at −40° C. for 1 h. The mixture was then transferred into a prewarmed (80° C.) solution of 6 M hydrogen chloride (18.49 mL, 110.93 mmol) and the mixture was stirred at 80° C. for 20 min. Water and DCM were added and the phases separated. The aqueous phase was extracted with DCM and the combined organic layers were filtered through a phase separator and evaporated. The compound was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×50 ID mm) using a gradient of 15-55% Acetonitrile in H2O/MeCN/FA 95/5/0.2 buffer over 30 minutes with a flow of 100 mL/min. The compounds were detected by UV at 220 nm. Cis-methyl 2-(4-chloro-3,5-difluorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.831 g, 62.3%) was yielded as colorless solid. 1H NMR (600 MHz, cdcl3) δ 1.80-1.87 (m, 1H), 2.04-2.15 (m, 1H), 2.19-2.28 (m, 1H), 2.30-2.36 (m, 1H), 3.00-3.09 (m, 1H), 3.30-3.39 (m, 1H), 3.66 (s, 3H), 4.07-4.16 (m, 1H), 4.98-5.05 (m, 1H), 5.59 (s, br., 1H), 6.80 (d, 2H). MS m/z 273 (M+H)+

Provenance & Evidence