Cis-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(4-fluorobenzyl)piperidine-1-carboxylate (2.53 g, 6.92 mmol) was dissolved in MeOH (20 mL) and cooled to −40° C. under nitrogen. Sodium hydroxide (0.277 g, 6.92 mmol) dissolved in water (2.000 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, 0.424 mL, 6.92 mmol) was added during 8 min. The resulting solution was stirred at −40° C. for 2 h. The mixture was then rapidly poured into a prewarmed (80° C.) solution of 6 M hydrogen chloride (30 mL, 180.00 mmol) and the mixture continued to stir at 80° C. for 20 min. The solvent was evaporated and DCM/water added. The phases were separated and the organic phase passed through a phase separator and evaporated to yield a yellow 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 0-35% Acetonitrile in H2O/MeCN/NH3 95/5/0.2 buffer over 20 minutes with a flow of 100 mL/min. Cis-methyl 2-(4-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (1.516 g, 65.5%) was isolated as a white solid. 1H NMR (400 MHz, cdcl3) δ 1.83-2.14 (m, 4H), 2.55-2.65 (m, 1H), 2.72-2.81 (m, 1H), 2.93-3.03 (m, 1H), 3.08-3.19 (m, 1H), 3.61 (s, 3H), 3.95-4.05 (m, 1H), 4.20-4.30 (m, 1H), 5.73 (s, 1H), 6.91-6.99 (m, 2H), 7.02-7.09 (m, 2H). MS m/z 335 (M+H)+
