Hydrochloric Acid → HCID 68502461, compound

Participants

Reaction Conditions

Reaction Steps

Cis-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(3-methyl-4-(trifluoromethyl)phenyl)piperidine-1-carboxylate (1.4 g, 3.37 mmol) was dissolved in MeOH (20 mL) and cooled to −40° C. NaOH (0.135 g, 3.37 mmol) dissolved in water (2 mL) was added during 10 min and the resulting colourless solution continued to stir at −40° C. for 20 min. Hydroxylamine (50% by weight in water, 0.223 g, 3.37 mmol) was added dropwise. The resulting solution was stirred at −40° C. for 30 min. The mixture was then transferred into a prewarmed (80° C.) solution of 6 M HCl and the mixture continued to stir at 80° C. for 20 min. The mixture was dissolved between diethyl ether and water. The phases were separated and the organic phase was dried over Na2SO4, filtered through celite and the solvent removed. Purified by preparative HPLC. Gradient eluation using acetonitrile-acidic buffer, started 40-60 and ended 55-45. Cis-methyl 2-(3-methyl-4-(trifluoromethyl)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (0.37 g, 29%) was isolated. 1H NMR (600 MHz, cdcl3) δ 1.80-1.87 (m, 1H), 2.07-2.28 (m, 2H), 2.31-2.38 (m, 1H), 2.41 (s, 3H), 3.03-3.10 (m, 1H), 3.35-3.43 (m, 1H), 3.66 (s, 3H), 4.13-4.19 (m, 1H), 5.09 (t, 1H), 5.52 (s, 1H), 7.02-7.06 (m, 2H), 7.49 (d, 1H). MS m/z 385 (M+H)+

Provenance & Evidence