Isopropanol heptane → HCID 86646614, compound

HRID 1963591Notes

Reaction equation

HRID 1963591 reaction equation
[CH3:1][S:2]([C:5]1[CH:27]=[CH:26][C:8]([CH2:9][CH:10]2[CH2:15][CH:14]([C:16]3[O:20][NH:19][C:18](=[O:21])[CH:17]=3)[CH2:13][CH2:12][N:11]2[C:22]([O:24][CH3:25])=[O:23])=[CH:7][CH:6]=1)(=[O:4])=[O:3].CCCCCCC.CC(O)C.CCCCCCC.CCO>C(#N)C>[CH3:1][S:2]([C:5]1[CH:27]=[CH:26][C:8]([CH2:9][C@H:10]2[CH2:15][C@@H:14]([C:16]3[O:20][NH:19][C:18](=[O:21])[CH:17]=3)[CH2:13][CH2:12][N:11]2[C:22]([O:24][CH3:25])=[O:23])=[CH:7][CH:6]=1)(=[O:4])=[O:3]

Participants

5

Reactant 3

HCID 21225753Isopropanol heptaneHCID 22502148Ethanol heptaneHCID 66731863HCID 66731863, compound

Product 1

HCID 86646614HCID 86646614, compoundYield 23.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Methyl 2-(4-(methylsulfonyl)benzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (1 g, 2.54 mmol) was subjected to chiral preparative HPLC in two steps (first using Column: Chiralcel OJ (250×50), 20 μm particle size, mobile phase: Heptane/IPA/FA 30/70/0.1, flow rate 120 mL/min and then using Column: Chiralpak AD (250×50), 20 μm particle size, mobile phase: Heptane/EtOH/FA 40/60/0.1, flow rate 120 mL/min) to yield (2R,4S)-Methyl 2-(4-(methylsulfonyl)benzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (231 mg, 23%), Chiral purity 99.5% ee, Optical rotation [α]D20=+10.1 (acetonitrile, c=1), 1H NMR (600 MHz, cdcl3) δ 1.87-1.97 (m, 3H), 2.02-2.11 (m, 1H), 2.68 (dd, 1H), 2.88 (dd, 1H), 2.96-3.06 (m, 4H), 3.12-3.22 (m, 1H), 3.60 (s, 3H), 3.96-4.02 (m, 1H), 4.27-4.35 (m, 1H), 5.74 (s, 1H), 7.30 (d, 2H), 7.82 (d, 2H); (2S,4R)-methyl 2-(4-(methylsulfonyl)benzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (225 mg, 22.5%), Chiral purity 98.4% ee, Optical rotation [α]D20=−11.4 (acetonitrile, c=1), 1H NMR (600 MHz, cdcl3) δ 1.86-1.97 (m, 3H), 2.02-2.10 (m, 1H), 2.67 (dd, 1H), 2.87 (dd, 1H), 2.96-3.05 (m, 4H), 3.12-3.20 (m, 1H), 3.59 (s, 3H), 3.95-4.02 (m, 1H), 4.27-4.34 (m, 1H), 5.74 (s, 1H), 7.29 (d, 2H), 7.81 (d, 2H) and trans-methyl 2-(4-(methylsulfonyl)benzyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (185 mg, 18.5%)

Sources & evidence

ORD record
ord-93e5ef07e3f641a1bb5e8680d90370e7
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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