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

HRID 1963597Notes

Reaction equation

HRID 1963597 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][C:24]=1[F:25])[CH2:5][C@H:6]1[CH2:11][C@@H:10]([C:12]2[O:16][NH:15][C:14](=[O:17])[CH:13]=2)[CH2:9][CH2:8][N:7]1[C:18]([O:20][CH3:21])=[O:19].CCCCCCC.CCO>C(#N)C>[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][C:24]=1[F:25])[CH2:5][C@H:6]1[CH2:11][C@@H:10]([C:12]2[O:16][NH:15][C:14](=[O:17])[CH:13]=2)[CH2:9][CH2:8][N:7]1[C:18]([O:20][CH3:21])=[O:19].[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][C:24]=1[F:25])[CH2:5][C@@H:6]1[CH2:11][C@H:10]([C:12]2[O:16][NH:15][C:14](=[O:17])[CH:13]=2)[CH2:9][CH2:8][N:7]1[C:18]([O:20][CH3:21])=[O:19]

Participants

5

Reactant 2

HCID 22502148Ethanol heptaneHCID 68506974(2R,4S)-Methyl 2-(3,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 2

HCID 66735150(2S,4R)-Methyl 2-(3,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylateYield 87.4%HCID 68506974(2R,4S)-Methyl 2-(3,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

Cis-methyl 2-(3,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (1.36 g, 3.87 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-(3,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (550 mg (40%), Chiral purity 98.2% ee, Optical rotation [α]D20=+15.0 (acetonitrile, c=1) and (2S,4R)-methyl 2-(3,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (596 mg, 44%), Chiral purity 99.4% ee, Optical rotation [α]D20=−13.2 (acetonitrile, c=1)

Sources & evidence

ORD record
ord-6f7c5fc9542b42f88d5cfacd08c07196
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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