Ethanol heptane → HCID 66732940, compound

HRID 1963446Notes

Reaction equation

HRID 1963446 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]=[C:21]([F:23])[C:20]([F:24])=[C:19]([F:25])[CH:18]=3)[CH2:8]2)[O:4][NH:3]1.CCCCCCC.CCO>C(#N)C>[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]=[C:21]([F:23])[C:20]([F:24])=[C:19]([F:25])[CH:18]=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:22]=[C:21]([F:23])[C:20]([F:24])=[C:19]([F:25])[CH:18]=3)[CH2:8]2)[O:4][NH:3]1

Participants

5

Reactant 2

HCID 22502148Ethanol heptaneHCID 66732940HCID 66732940, compound

Product 2

HCID 66732940HCID 66732940, compoundYield 46%HCID 68502355HCID 68502355, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

Cis-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3,4,5-trifluorophenyl)piperidine-1-carboxylate (355 mg, 1 mmol) was subjected to chiral preparative HPLC (Column: CelluCoat (250×20), 5 μm particle size, mobile phase: Heptane/EtOH 60/40, flow rate 18 mL/min) to yield (2R,4S)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3,4,5-trifluorophenyl)piperidine-1-carboxylate (164 mg, 46%), Chiral purity 98.7% ee, Optical rotation [α]D20=+60.6 (acetonitrile, c=0.5), 1H NMR (400 MHz, cdcl3) δ 1.80-1.90 (m, 1H), 1.99-2.40 (m, 3H), 3.00-3.13 (m, 1H), 3.29-3.42 (m, 1H), 3.69 (s, 3H), 4.07-4.19 (m, 1H), 4.97-5.07 (m, 1H), 5.60 (s, 1H), 6.75-6.85 (m, 2H), and (2S,4R)-methyl 4-(3-oxo-2,3-dihydroisoxazol-5-yl)-2-(3,4,5-trifluorophenyl)piperidine-1-carboxylate (160 mg, 45%), Chiral purity 99.9% ee, Optical rotation [α]D20=−52.9 (acetonitrile, c=1), 1H NMR (400 MHz, cdcl3) δ 1.81-1.90 (m, 1H), 2.05-2.15 (m, 1H), 2.19-2.38 (m, 2H), 3.02-3.11 (m, 1H), 3.30-3.40 (m, 1H), 3.69 (s, 3H), 4.09-4.18 (m, 1H), 4.99-5.05 (m, 1H), 5.60 (s, 1H), 6.76-6.84 (m, 2H).

Sources & evidence

ORD record
ord-8986fa36c0d74765b41b7c5790f71d18
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

Loading…