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

HRID 1963554Notes

Reaction equation

HRID 1963554 reaction equation
[F:1][C:2]1[CH:24]=[CH:23][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].CCO.C(#N)C>C(=O)=O>[F:1][C:2]1[CH:24]=[CH:23][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]=[CH:23][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

6

Reactant 3

HCID 702EthanolHCID 6342Acetonitrile2×HCID 66732693(2R,4R)-Methyl 2-(2-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 2

HCID 66732457(2S,4S)-Methyl 2-(2-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylateYield 43%HCID 66732693(2R,4R)-Methyl 2-(2-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylateYield 40%

Reagents, catalysts & solvents 1

HCID 280Carbon DioxideSolvent

Procedure

Trans-methyl 2-(2-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (468 mg, 1.4 mmol) was subjected to chiral preparative HPLC (Column: Chiralcel OJ (250×30), 5 μm particle size, mobile phase: 20% EtOH in CO2 (175 bar), flow rate 130 mL/min, temperature 40° C.) to yield (2S,4S)-methyl 2-(2-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (199 mg, 43%), Chiral purity 98.5% ee, Optical rotation [α]D20=+28.8 (acetonitrile, c=1) and (2R,4R)-methyl 2-(2-fluorobenzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (185 mg, 40%), Chiral purity 99.7% ee, Optical rotation [α]D20=−28.9 (acetonitrile, c=1)

Sources & evidence

ORD record
ord-3a91bfefcc2642fcb8c8726571e4ee3f
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

Loading…