Ethanol → Ethyl 3-(4,5-dimethyl-4H-1,2,4-triazol-3-yl)-2-(4-fluorophenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate

HRID 907919Notes

Reaction equation

HRID 907919 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.[CH3:20][N:21]1[C:25]([CH3:26])=[N:24][N:23]=[C:22]1[CH:27]=O.[O-:29][CH2:30][CH3:31].[Na+].C(O)C>C(OCC)(=O)CC.C(OCC)(=O)C.CO>[CH3:20][N:21]1[C:25]([CH3:26])=[N:24][N:23]=[C:22]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

Participants

7

Reactant 4

HCID 702EthanolHCID 2723922Sodium ethoxideHCID 552536594,5-dimethyl-4H-1,2,4-triazole-3-carbaldehydeHCID 178519076HCID 178519076, compound

Product 1

HCID 67261517Ethyl 3-(4,5-dimethyl-4H-1,2,4-triazol-3-yl)-2-(4-fluorophenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylateYield 21%

Reagents, catalysts & solvents 2

HCID 7749Ethyl PropionateSolventHCID 21584119Ethylacetate methanolSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of (E)-4-(4-fluorobenzylideneamino)isobenzofuran-1(3H)-one (510 mg, 2 mmol) and 4,5-dimethyl-4H-1,2,4-triazole-3-carbaldehyde (275 mg, 2.2 mmol) in ethyl propionate (20 mL) was cooled to 0° C. Then a solution of sodium ethoxide in ethanol (sodium (184 mg, 8 mmol) in ethanol (10 mL)) was added dropwise. After the addition, the mixture was stirred at 10° C. for 2 hr, then 30° C. 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 (30 mL×4). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated to give a crude product. The crude product was purified by chromatography (silica gel, petroleum ether/ethyl acetate=3:1 then ethyl acetate/methanol=30:1) to afford the title compound (170 mg, yield: 21%). LC-MS (ESI) m/z: 409 (M+1)+.

Workup

  1. additionAfter the addition
  2. wait30° C. for 4 hr
  3. customThe mixture was quenched with water (10 mL) and solvent
  4. customwas removed in vacuum
  5. dissolutionThe residue was dissolved in water
  6. extractionextracted with ethyl acetate (30 mL×4)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated
  10. customto give a crude product
  11. customThe crude product was purified by chromatography (silica gel, petroleum ether/ethyl acetate=3:1

Sources & evidence

ORD record
ord-77d6fbc22da74657ae38d2f0557bc64c
Source dataset
uspto-grants-2011_09
Patent number
US08012976B2

Reaction notes

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