Isopropanol heptane → HCID 68502461, compound

HRID 1963463Notes

Reaction equation

HRID 1963463 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C@H:12]2[CH2:17][C@@H:16]([C:18]3[O:22][NH:21][C:20](=[O:23])[CH:19]=3)[CH2:15][CH2:14][N:13]2[C:24]([O:26][CH3:27])=[O:25])[CH:5]=[CH:6][C:7]=1[C:8]([F:11])([F:10])[F:9].CCCCCCC.CC(O)C>C(#N)C>[CH3:1][C:2]1[CH:3]=[C:4]([C@H:12]2[CH2:17][C@@H:16]([C:18]3[O:22][NH:21][C:20](=[O:23])[CH:19]=3)[CH2:15][CH2:14][N:13]2[C:24]([O:26][CH3:27])=[O:25])[CH:5]=[CH:6][C:7]=1[C:8]([F:9])([F:10])[F:11].[CH3:1][C:2]1[CH:3]=[C:4]([C@@H:12]2[CH2:17][C@H:16]([C:18]3[O:22][NH:21][C:20](=[O:23])[CH:19]=3)[CH2:15][CH2:14][N:13]2[C:24]([O:26][CH3:27])=[O:25])[CH:5]=[CH:6][C:7]=1[C:8]([F:9])([F:10])[F:11]

Participants

5

Reactant 2

HCID 21225753Isopropanol heptaneHCID 68502461HCID 68502461, compound

Product 2

HCID 66732784HCID 66732784, compoundYield 45%HCID 68502461HCID 68502461, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

Cis-methyl 2-(3-methyl-4-(trifluoromethyl)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)-piperidine-1-carboxylate (0.37 g, 0.96 mmol) was subjected to chiral preparative HPLC (Column: CelluCoat OJ (250×50), 10 μm particle size, mobile phase: Heptane/EtOH 50/50, flow rate 120 mL/min) to yield (2R,4S)-methyl 2-(3-methyl-4-(trifluoromethyl)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (177 mg, 48%), Chiral purity 99.2% ee, Optical rotation [α]D20=+57.1 (acetonitrile, c=1), 1H NMR (600 MHz, cdcl3) δ 1.78-1.85 (m, 1H), 2.08-2.16 (m, 1H), 2.17-2.26 (m, 1H), 2.29-2.36 (m, 1H), 2.39 (s, 3H), 3.01-3.09 (m, 1H), 3.34-3.42 (m, 1H), 3.64 (s, 3H), 4.09-4.17 (m, 1H), 5.07 (t, 1H), 5.50 (s, 1H), 7.01-7.07 (m, 2H), 7.47 (d, 1H), 10.63 (br, 1H), and (2S,4R)-methyl 2-(3-methyl-4-(trifluoromethyl)phenyl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (168 mg, 45%), Chiral purity 99.9% ee, Optical rotation [α]D20=−57.1 (acetonitrile, c=1), 1H NMR (600 MHz, cdcl3) δ 1.79-1.86 (m, 1H), 2.10-2.18 (m, 1H), 2.19-2.27 (m, 1H), 2.31-2.37 (m, 1H), 2.41 (s, 3H), 3.02-3.09 (m, 1H), 3.35-3.42 (m, 1H), 3.65 (s, 3H), 4.11-4.18 (m, 1H), 5.08 (t, 1H), 5.51 (s, 1H), 7.02-7.07 (m, 2H), 7.48 (d, 1H).

Sources & evidence

ORD record
ord-9462bd62d7a4487da78528584fc09b89
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

Loading…