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

HRID 1963601Notes

Reaction equation

HRID 1963601 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>[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

4

Reactant 1

HCID 68502241(2R,4R)-Methyl 2-(3,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 2

HCID 68501682(2S,4S)-Methyl 2-(3,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylateYield 54%HCID 68502241(2R,4R)-Methyl 2-(3,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylateYield 38%

Reagents, catalysts & solvents 1

HCID 8900HeptaneSolvent

Procedure

Trans-methyl 2-(3,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (83 mg, 0.24 mmol) was subjected to chiral preparative HPLC (Column: ReproSil (250×20), 8 μm particle size, mobile phase: Heptane/(MTBE/MeOH 95/5) 70/30, flow rate 18 mL/min) to yield (2S,4S)-methyl 2-(3,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (45 mg, 54%), Chiral purity 99.6% ee and (2R,4R)-methyl 2-(3,4-difluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (32 mg, 38%), Chiral purity 99.9% ee.

Sources & evidence

ORD record
ord-47f04636a9ee4ca98d2c28a14933d06c
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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