Hydrochloric Acid → HCID 68501466, compound

Participants

Reaction Conditions

Reaction Steps

Cis-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(2-fluoro-4-(trifluoromethoxy)phenyl)piperidine-1-carboxylate (3.22 g, 7.40 mmol) was dissolved in MeOH (30 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (0.311 g, 7.77 mmol) dissolved in water (3.00 mL) was added and the mixture was stirred at −40° C. for 15 min. Hydroxylamine (50% by weight in water, 0.476 mL, 7.77 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 (38.2 mL, 229.28 mmol) and the mixture was stirred at 80° C. for 15 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 (4 runs) (10 μm 250×50 ID mm) using a gradient of 25-65% Acetonitrile in H2O/MeCN/HOAc 95/5/0.2 buffer over 25 minutes with a flow of 100 mL/min. Cis-methyl 2-(2-fluoro-4-(trifluoromethoxy)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (1.82 g, 61%) was isolated. 1H NMR (600 MHz, cdcl3) δ 1.82-1.91 (m, 1H), 2.03-2.13 (m, 1H), 2.22-2.41 (m, 2H), 3.01-3.10 (m, 1H), 3.43-3.53 (m, 1H), 3.63 (s, 3H), 4.11-4.21 (m, 1H), 5.19 (dd, 1H), 5.59 (s, 1H), 6.89-6.95 (m, 2H), 7.14 (t, 1H). MS m/z 405 (M+H)+

Provenance & Evidence