Isopropanol heptane → (2R,4S)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate

HRID 1963453Notes

Reaction equation

HRID 1963453 reaction equation
[O:1]=[C:2]1[CH:6]=[C:5]([C@H:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][CH3:16])=[O:14])[C@@H:9]([C:17]3[CH:22]=[C:21]([F:23])[C:20]([F:24])=[CH:19][C:18]=3[F:25])[CH2:8]2)[O:4][NH:3]1.[O:26]=[C:27]1[CH:31]=[C:30]([C@@H:32]2[CH2:37][CH2:36][N:35]([C:38]([O:40][CH3:41])=[O:39])[C@@H:34]([C:42]3[CH:47]=[C:46]([F:48])[C:45]([F:49])=[CH:44][C:43]=3[F:50])[CH2:33]2)[O:29][NH:28]1.CCCCCCC.CC(O)C>C(#N)C>[O:1]=[C:2]1[CH:6]=[C:5]([C@H:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][CH3:16])=[O:14])[C@@H:9]([C:17]3[CH:22]=[C:21]([F:23])[C:20]([F:24])=[CH:19][C:18]=3[F:25])[CH2:8]2)[O:4][NH:3]1.[O:26]=[C:27]1[CH:31]=[C:30]([C@H:32]2[CH2:37][CH2:36][N:35]([C:38]([O:40][CH3:41])=[O:39])[C@H:34]([C:42]3[CH:47]=[C:46]([F:48])[C:45]([F:49])=[CH:44][C:43]=3[F:50])[CH2:33]2)[O:29][NH:28]1

Participants

6

Reactant 3

HCID 21225753Isopropanol heptaneHCID 68503549(2R,4S)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylateHCID 131730420trans-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate

Product 2

HCID 66732279(2S,4S)-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylateYield 20%HCID 68503549(2R,4S)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylateYield 25%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

The mixture of cis-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)-piperidine-1-carboxylate and trans-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate (1.027 g, 2.88 mmol) was subjected to chiral preparative HPLC (Column: CelluCoat (250×20), 5 μm particle size, mobile phase: Heptane/IPA 80/20, flow rate 18 mL/min) to yield (2R,4S)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate (259 mg, 25%), Chiral purity A % 99.9, Optical rotation [α]D20=+50.3 (acetonitrile, c=1), and (2S,4S)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(2,4,5-trifluorophenyl)piperidine-1-carboxylate (203 mg, 20%), Chiral purity A %: 99.9, Optical rotation [α]D20=+4.5 (acetonitrile, c=1)

Sources & evidence

ORD record
ord-f3922d264b2b4be8afd4e389601f9938
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

Loading…