Ethanol → ethyl 7-fluoro-3-(1-methyl-1H-imidazol-2-yl)-4-oxo-2-phenyl-1,2,3,4-tetrahydroquinoline-5-carboxylate

HRID 1467579Notes

Reaction equation

HRID 1467579 reaction equation
[CH:1](=[N:8]/[C:9]1[CH:17]=[C:16]([F:18])[CH:15]=[C:14]2[C:10]=1[CH2:11][O:12][C:13]2=[O:19])\[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:20][N:21]1[CH:25]=[CH:24][N:23]=[C:22]1[CH:26]=O.[O-:28][CH2:29][CH3:30].[Na+].C(O)C>C(OCC)(=O)CC>[F:18][C:16]1[CH:15]=[C:14]([C:13]([O:12][CH2:11][CH3:10])=[O:19])[C:30]2[C:29](=[O:28])[CH:26]([C:22]3[N:21]([CH3:20])[CH:25]=[CH:24][N:23]=3)[CH:1]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[NH:8][C:9]=2[CH:17]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 1395751-Methyl-2-imidazolecarboxaldehydeHCID 2723922Sodium ethoxideHCID 178519071HCID 178519071, compound

Product 1

HCID 67261321ethyl 7-fluoro-3-(1-methyl-1H-imidazol-2-yl)-4-oxo-2-phenyl-1,2,3,4-tetrahydroquinoline-5-carboxylate

Reagents, catalysts & solvents 1

HCID 7749Ethyl PropionateSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of (E)-4-(benzylideneamino)-6-fluoroisobenzofuran-1(3H)-one (2 g, 7.8 mmol) and 1-methyl-1H-imidazole-2-carbaldehyde (0.949 g, 8.63 mmol) in ethyl propionate (50 mL) was cooled to 0° C. Then a solution of sodium ethoxide in ethanol [sodium (722 mg, 31.37 mmol) in ethanol (30 mL)] was added drop-wise. 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=10:1 to 1:10) to give the ethyl 7-fluoro-3-(1-methyl-1H-imidazol-2-yl)-4-oxo-2-phenyl-1,2,3,4-tetrahydroquinoline-5-carboxylate (141 mg). 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 1.18-1.22 (t, 3H), 3.31 (s, 3H), 4.17-4.21 (q, 2H), 4.621-4.65 (d, 2H), 5.17-5.20 (d, 1H), 6.48-6.51 (dd, 1H), 6.70-6.73 (m, 2H), 6.86 (s, 1H), 7.24-7.30 (m, 3 H), 7.42-7.44 (t, 2H), 7.76 (s, 1H); LC-MS (ESI) m/z: 394 (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=10:1 to 1:10)

Sources & evidence

ORD record
ord-9a01bea15ab34f9c9893d3324cdcdc2b
Source dataset
uspto-grants-2015_04
Patent number
US08999987B2

Reaction notes

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