Sodium ethoxide → Ethyl 3-(1-ethyl-1H-imidazol-2-yl)-2-(4-fluorophenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate

HRID 907934Notes

Reaction equation

HRID 907934 reaction equation
[F:1][C:2]1[CH:19]=[CH:18][C:5](/[CH:6]=[N:7]/[C:8]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:9]=2[CH2:10][O:11][C:12]3=[O:17])=[CH:4][CH:3]=1.[CH2:20]([N:22]1[CH:26]=[CH:25][N:24]=[C:23]1[CH:27]=O)[CH3:21].[O-:29][CH2:30][CH3:31].[Na+]>C(OCC)(=O)CC>[CH2:20]([N:22]1[CH:26]=[CH:25][N:24]=[C:23]1[CH:27]1[C:30](=[O:29])[C:31]2[C:13]([C:12]([O:11][CH2:10][CH3:9])=[O:17])=[CH:14][CH:15]=[CH:16][C:8]=2[NH:7][CH:6]1[C:5]1[CH:18]=[CH:19][C:2]([F:1])=[CH:3][CH:4]=1)[CH3:21]

Participants

5

Reactant 3

HCID 2723922Sodium ethoxideHCID 110623771-ethyl-1H-imidazole-2-carbaldehydeHCID 178519076HCID 178519076, compound

Product 1

HCID 67261879Ethyl 3-(1-ethyl-1H-imidazol-2-yl)-2-(4-fluorophenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylateYield 7.4%

Reagents, catalysts & solvents 1

HCID 7749Ethyl PropionateSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of (E)-4-(4-fluorobenzylideneamino)isobenzofuran-1(3H)-one (765 mg, 3 mmol) and N-ethyl-2-imidazolecarbaldehyde (372 mg, 3 mmol) in ethyl propionate (45 mL) was cooled to 0° C. Then a solution of sodium ethoxide (sodium (276 mg, 12 mmol) in ethanol (45 mL)) was added dropwise. After the addition, the mixture was stirred at room temperature for 4 hr. The mixture was quenched with water (10 mL) and solvent was removed in vacuum. The residue was dissolved in water, and then extracted with ethyl acetate (100 mL×4). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated to give crude product. The crude product was purified by chromatography (silica gel, petroleum ether/ethyl acetate=25:1 to 5:1) to give the title compound (90 mg, yield: 7%). LC-MS (ESI) m/z: 408 (M+1)+.

Workup

  1. additionAfter the addition
  2. customThe mixture was quenched with water (10 mL) and solvent
  3. customwas removed in vacuum
  4. dissolutionThe residue was dissolved in water
  5. extractionextracted with ethyl acetate (100 mL×4)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. customto give crude product
  10. customThe crude product was purified by chromatography (silica gel, petroleum ether/ethyl acetate=25:1 to 5:1)

Sources & evidence

ORD record
ord-d891a99d9d9648a5834414fb9a69f7c7
Source dataset
uspto-grants-2011_09
Patent number
US08012976B2

Reaction notes

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