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

HRID 1963383Notes

Reaction equation

HRID 1963383 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]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=3)[CH2:8]2)[O:4][NH:3]1.CO.C(#N)C>C(=O)=O>[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:18]=[CH:19][C:20]([C:23]([F:26])([F:24])[F:25])=[CH:21][CH:22]=3)[CH2:8]2)[O:4][NH:3]1.[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:18]=[CH:19][C:20]([C:23]([F:26])([F:24])[F:25])=[CH:21][CH:22]=3)[CH2:8]2)[O:4][NH:3]1

Participants

6

Reactant 3

HCID 887MethanolHCID 6342Acetonitrile2×HCID 66739070(2R,4S)-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(4-(trifluoromethyl)phenyl)piperidine-1-carboxylate

Product 2

HCID 66735438(2S,4R)-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(4-(trifluoromethyl)phenyl)piperidine-1-carboxylateYield 35%HCID 66739070(2R,4S)-Methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(4-(trifluoromethyl)phenyl)piperidine-1-carboxylateYield 34%

Reagents, catalysts & solvents 1

HCID 280Carbon DioxideSolvent

Procedure

Cis-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(4-(trifluoromethyl)phenyl)piperidine-1-carboxylate (1.682 g, 4.54 mmol) was subjected to chiral preparative HPLC (Column: Chiralpak IA (250×30), 5 μm particle size, mobile phase: 15% MeOH in CO2 (175 bar), flow rate 130 mL/min, temperature 40° C.) to yield (2R,4S)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(4-(trifluoromethyl)phenyl)piperidine-1-carboxylate (580 mg, 34%), Chiral purity 99.9% ee, Optical rotation [α]D20=+53.3 (acetonitrile, c=1) and (2S,4R)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(4-(trifluoromethyl)phenyl)piperidine-1-carboxylate (591 mg, 35%), Chiral purity 98.8% ee, Optical rotation [α]D20=−74.2 (acetonitrile, c=1)

Sources & evidence

ORD record
ord-72805c68af3b4bc7b910dc4ac931fc61
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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