Ethanol → Ethyl 1,2,3,4-tetrahydro-3-(1-methyl-1H-imidazol-2-yl)-4-oxo-2-[4-(trifluoromethyl)phenyl]-5-quinolinecarboxylate

HRID 1968048Notes

Reaction equation

HRID 1968048 reaction equation
[F:1][C:2]([F:22])([F:21])[C:3]1[CH:20]=[CH:19][C:6](/[CH:7]=[N:8]/[C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH2:11][O:12][C:13]3=[O:18])=[CH:5][CH:4]=1.[CH3:23][N:24]1[CH:28]=[CH:27][N:26]=[C:25]1[CH:29]=O.[O-:31][CH2:32][CH3:33].[Na+].C(O)C>C(OCC)(=O)CC>[CH3:23][N:24]1[CH:28]=[CH:27][N:26]=[C:25]1[CH:29]1[C:11](=[O:12])[C:10]2[C:14]([C:13]([O:31][CH2:32][CH3:33])=[O:18])=[CH:15][CH:16]=[CH:17][C:9]=2[NH:8][CH:7]1[C:6]1[CH:5]=[CH:4][C:3]([C:2]([F:21])([F:1])[F:22])=[CH:20][CH:19]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 1395751-Methyl-2-imidazolecarboxaldehydeHCID 2723922Sodium ethoxideHCID 178519072HCID 178519072, compound

Product 1

HCID 67260485Ethyl 1,2,3,4-tetrahydro-3-(1-methyl-1H-imidazol-2-yl)-4-oxo-2-[4-(trifluoromethyl)phenyl]-5-quinolinecarboxylateYield 8%

Reagents, catalysts & solvents 1

HCID 7749Ethyl PropionateSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of (E)-4-(4-(trifluoromethyl)benzylideneamino)isobenzofuran-1(3H)-one (1 g, 3.28 mmol) and N-methyl-2-imidazolecarbaldehyde (400 mg, 3.61 mmol) in ethyl propionate (40 mL) was cooled to 0° C. Then a solution of sodium ethoxide in ethanol (sodium (31 mg, 13.1 mmol) in ethanol (10 mL)) was added dropwise. After the addition, the mixture was stirred at room temperature for 2 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=1:1) to give the title compound (150 mg, yield 8%). LC-MS (ESI) m/z: 444 (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=1:1)

Sources & evidence

ORD record
ord-302172e3701e4cc192fe46b188c5c6d1
Source dataset
uspto-grants-2013_04
Patent number
US08420650B2

Reaction notes

Loading…