Reaction Steps
Cis-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3,4,5-trifluorophenyl)piperidine-1-carboxylate (355 mg, 1 mmol) was subjected to chiral preparative HPLC (Column: CelluCoat (250×20), 5 μm particle size, mobile phase: Heptane/EtOH 60/40, flow rate 18 mL/min) to yield (2R,4S)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3,4,5-trifluorophenyl)piperidine-1-carboxylate (164 mg, 46%), Chiral purity 98.7% ee, Optical rotation [α]D20=+60.6 (acetonitrile, c=0.5), 1H NMR (400 MHz, cdcl3) δ 1.80-1.90 (m, 1H), 1.99-2.40 (m, 3H), 3.00-3.13 (m, 1H), 3.29-3.42 (m, 1H), 3.69 (s, 3H), 4.07-4.19 (m, 1H), 4.97-5.07 (m, 1H), 5.60 (s, 1H), 6.75-6.85 (m, 2H), and (2S,4R)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3,4,5-trifluorophenyl)piperidine-1-carboxylate (160 mg, 45%), Chiral purity 99.9% ee, Optical rotation [α]D20=−52.9 (acetonitrile, c=1), 1H NMR (400 MHz, cdcl3) δ 1.81-1.90 (m, 1H), 2.05-2.15 (m, 1H), 2.19-2.38 (m, 2H), 3.02-3.11 (m, 1H), 3.30-3.40 (m, 1H), 3.69 (s, 3H), 4.09-4.18 (m, 1H), 4.99-5.05 (m, 1H), 5.60 (s, 1H), 6.76-6.84 (m, 2H).
