Ethanol heptane → (2R,4S)-Methyl 2-(2,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

HRID 1963627Notes

Reaction equation

HRID 1963627 reaction equation
[F:1][C:2]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:3]=1[CH2:4][C@H:5]1[CH2:10][C@@H:9]([C:11]2[O:15][NH:14][C:13](=[O:16])[CH:12]=2)[CH2:8][CH2:7][N:6]1[C:17]([O:19][CH3:20])=[O:18].CCCCCCC.CCO>C(#N)C>[F:1][C:2]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:3]=1[CH2:4][C@H:5]1[CH2:10][C@@H:9]([C:11]2[O:15][NH:14][C:13](=[O:16])[CH:12]=2)[CH2:8][CH2:7][N:6]1[C:17]([O:19][CH3:20])=[O:18].[F:1][C:2]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:3]=1[CH2:4][C@@H:5]1[CH2:10][C@H:9]([C:11]2[O:15][NH:14][C:13](=[O:16])[CH:12]=2)[CH2:8][CH2:7][N:6]1[C:17]([O:19][CH3:20])=[O:18]

Participants

5

Reactant 2

HCID 22502148Ethanol heptaneHCID 68502687(2R,4S)-Methyl 2-(2,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 2

HCID 66734591(2S,4R)-Methyl 2-(2,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylateYield 45%HCID 68502687(2R,4S)-Methyl 2-(2,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylateYield 49%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

Cis-methyl 2-(2,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (1.62 g, 4.6 mmol) was subjected to chiral preparative HPLC (Column: Chiralpak AD (250×20), 5 μm particle size, mobile phase: Heptane/EtOH/FA 90/10/0.2, flow rate 18 mL/min) to yield (2R,4S)-methyl 2-(2,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (799 mg, 49%), Chiral purity 99.9% ee, Optical rotation [α]D20=−4.0 (acetonitrile, c=1) and (2S,4R)-methyl 2-(2,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (734 mg, 45%), Chiral purity 99.5% ee, Optical rotation [α]D20=+4.5 (acetonitrile, c=1).

Sources & evidence

ORD record
ord-3791b331cf0e416e9447039e15c6094b
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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