Isopropanol heptane → (2R,4R)-Methyl 2-(4-fluorophenethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

HRID 1963527Notes

Reaction equation

HRID 1963527 reaction equation
[F:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][CH2:7][C@H:8]2[CH2:13][C@@H:12]([C:14]3[O:18][NH:17][C:16](=[O:19])[CH:15]=3)[CH2:11][CH2:10][N:9]2[C:20]([O:22][CH3:23])=[O:21])=[CH:4][CH:3]=1.CCCCCCC.CC(O)C>C(#N)C>[F:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][CH2:7][C@H:8]2[CH2:13][C@@H:12]([C:14]3[O:18][NH:17][C:16](=[O:19])[CH:15]=3)[CH2:11][CH2:10][N:9]2[C:20]([O:22][CH3:23])=[O:21])=[CH:4][CH:3]=1.[F:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][CH2:7][C@@H:8]2[CH2:13][C@H:12]([C:14]3[O:18][NH:17][C:16](=[O:19])[CH:15]=3)[CH2:11][CH2:10][N:9]2[C:20]([O:22][CH3:23])=[O:21])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 21225753Isopropanol heptaneHCID 68502316(2S,4S)-Methyl 2-(4-fluorophenethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate

Product 2

HCID 66732238(2R,4R)-Methyl 2-(4-fluorophenethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylateYield 48%HCID 68502316(2S,4S)-Methyl 2-(4-fluorophenethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylateYield 42%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

Cis-methyl 2-(4-fluorophenethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (1.4 g, 4 mmol) was subjected to chiral preparative HPLC (Column: Chiralpak AD (250×20), 5 μm particle size, mobile phase: Heptane/EtOH 80/20, flow rate 18 mL/min) to yield (2S,4S)-methyl 2-(4-fluorophenethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (582 mg, 42%), Chiral purity 99.9% ee, Optical rotation [α]D20=+51.6 (acetonitrile, c=1) and (2R,4R)-methyl 2-(4-fluorophenethyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (676 mg, 48%), Chiral purity 99.4% ee, Optical rotation [α]D20=−45.0 (acetonitrile, c=1)

Sources & evidence

ORD record
ord-0366a8b7e3df4da990e4b7eb65c00e04
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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