Ethanol → HCID 66732221, compound
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:13][C@@H:12]([C:14]3[O:18][NH:17][C:16](=[O:19])[CH:15]=3)[CH2:11][CH2:10][N:9]2[C:20]([O:22][CH3:23])=[O:21])=[CH:4][CH:3]=1.CCO>C(#N)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:13][C@@H:12]([C:14]3[O:18][NH:17][C:16](=[O:19])[CH:15]=3)[CH2:11][CH2:10][N:9]2[C:20]([O:22][CH3:23])=[O:21])=[CH:4][CH:3]=1.[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:13][C@H:12]([C:14]3[O:18][NH:17][C:16](=[O:19])[CH:15]=3)[CH2:11][CH2:10][N:9]2[C:20]([O:22][CH3:23])=[O:21])=[CH:4][CH:3]=1Participants
Reactant 2
Product 2
Reagents, catalysts & solvents 1
Procedure
Cis-methyl 2-(4-chlorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (923 mg, 2.75 mmol) was subjected to chiral preparative HPLC (Column: ReproSil (250×50), 8 μm particle size, mobile phase: EtOH, flow rate 100 mL/min) to yield (2R,4S)-methyl 2-(4-chlorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (447 mg, 48%), Chiral purity 99.9% ee, Optical rotation [α]D20=+67.7 (acetonitrile, c=1), 1H NMR (400 MHz, cdcl3) δ 1.79-1.89 (m, 1H), 2.07-2.40 (m, 3H), 3.01-3.11 (m, 1H), 3.33-3.43 (m, 1H), 3.66 (s, 3H), 4.10-4.19 (m, 1H), 5.07 (dd, 1H), 5.55 (s, 1H), 7.08-7.14 (m, 2H), 7.23-7.28 (m, 2H) and (2S,4R)-methyl 2-(4-chlorophenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)-piperidine-1-carboxylate (458 mg, 49%), Chiral purity 99.6% ee, Optical rotation [α]D20=−67.6 (acetonitrile, c=1), 1H NMR (400 MHz, cdcl3) δ 1.79-1.88 (m, 1H), 2.07-2.38 (m, 3H), 3.02-3.10 (m, 1H), 3.33-3.43 (m, 1H), 3.66 (s, 3H), 4.11-4.18 (m, 1H), 5.04-5.09 (m, 1H), 5.54 (s, 1H), 7.09-7.13 (m, 2H), 7.23-7.28 (m, 2H).
Sources & evidence
- ORD record
- ord-371f6f6c487649c89da7ed75421523bc
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08415378B2
Reaction notes
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