Sodium Methoxide → 1-(2,4-Dimethoxybenzyl)-4-(3-fluorophenyl)-6-methoxy-2-oxo-1,2-dihydroquinoline-3-carbonitrile

HRID 640716Notes

Reaction equation

HRID 640716 reaction equation
[C:1]([CH2:3][C:4]([N:6]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][C:26]=1[O:33][CH3:34])[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][C:8]=1[C:15](=O)[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=1)=[O:5])#[N:2].C[O-].[Na+]>CO>[CH3:34][O:33][C:26]1[CH:27]=[C:28]([O:31][CH3:32])[CH:29]=[CH:30][C:25]=1[CH2:24][N:6]1[C:7]2[C:8](=[CH:9][C:10]([O:13][CH3:14])=[CH:11][CH:12]=2)[C:15]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)=[C:3]([C:1]#[N:2])[C:4]1=[O:5]

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 686597692-Cyano-N-(2,4-dimethoxybenzyl)-N-[2-(3-fluorobenzoyl)-4-methoxyphenyl]acetamide

Product 1

HCID 112707271-(2,4-Dimethoxybenzyl)-4-(3-fluorophenyl)-6-methoxy-2-oxo-1,2-dihydroquinoline-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To solution of 2-cyano-N-(2,4-dimethoxybenzyl)-N-[2-(3-fluorobenzoyl)-4-methoxyphenyl]acetamide (56.0 mg, 0.121 mmol) in 1 mL of methanol was added sodium methoxide solution in methanol (0.083 mL of 4.37 M, 0.363 mmol). The solution was heated to reflux for 5 minutes, then cooled to room temperature. The reaction was partitioned between EtOAc and water, and the organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by flash chomatography through SiO2 (30-50% EtOAc/hexane) to provide the titled product as a yellow foam. 1H-NMR (500 MHz, CDCl3) δ 7.56-7.60 (m, 1H), 7.39 (d, J=9.5 Hz, 1H), 7.25-7.31 (m, 2H), 7.17-7.21 (m, 2H), 6.91 (d, J=8.5 Hz, 1H), 6.74 (br s, 1H), 6.52 (br s, 1H), 6.38 (br d, J=8.5 Hz, 1H), 5.54 (s, 2H), 3.95 (s, 3H), 3.77 (s, 3H), 3.67 (s, 3H) ppm. HRMS (ES) exact mass calculated for C26H22FN2O4 (M+H+): 445.1558. Found 445.1574.

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux for 5 minutes
  3. customThe reaction was partitioned between EtOAc and water
  4. washthe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude residue was purified by flash chomatography through SiO2 (30-50% EtOAc/hexane)

Sources & evidence

ORD record
ord-f35df93158f54b06b7583044eeda59b3
Source dataset
uspto-grants-2010_04
Patent number
US07692017B2

Reaction notes

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