Ethyl Acrylate → ethyl 3-(2-oxo-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)propanoate

HRID 1183776Notes

Reaction equation

HRID 1183776 reaction equation
[F:1][C:2]([F:21])([F:20])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[NH:15][C:14](=[O:19])[CH2:13][CH2:12]3)=[CH:5][CH:4]=1.[OH-].[Na+].[C:24]([O:28][CH2:29][CH3:30])(=[O:27])[CH:25]=[CH2:26]>O1CCCC1.CN(C)C=O>[O:19]=[C:14]1[CH2:13][CH2:12][C:11]2[C:16](=[CH:17][CH:18]=[C:9]([C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:20])[F:21])=[CH:8][CH:7]=3)[CH:10]=2)[N:15]1[CH2:26][CH2:25][C:24]([O:28][CH2:29][CH3:30])=[O:27]

Participants

6

Reactant 3

HCID 8821Ethyl AcrylateHCID 14798Sodium Hydroxide2×HCID 120009366-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-2(1H)-one

Product 1

HCID 59316602ethyl 3-(2-oxo-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)propanoateYield 58%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-2(1H)-one, prepared as described above (90 mg, 0.31 mmol) in anhydrous tetrahydrofuran (3 mL) was added at room temperature 20-40 mesh beads of sodium hydroxide (48 mg, 1.20 mmol) and ethyl acrylate (1.200 g, 1.20 mmol) in anhydrous N,N-dimethylformamide (1 mL). The reaction mixture was stirred for 4 hours under an atmosphere of dry N2, followed by addition of a second portion of sodium hydroxide (96 mg, 2.40 mmol). The reaction was followed by LCMS and stirring was continued until all of the starting material had disappeared. Solvent was removed from the reaction mixture under reduced pressure, diluted with ethyl acetate (20 mL), and aqueous Na2SO3 (10 mL) added. The aqueous phase was extracted with ethyl acetate (3×20 mL), and the combined organic phase successively washed with 2N sodium carbonate (20 mL), 30% ammonium chloride (20 mL), brine (20 mL), and dried over magnesium sulfate. Evaporation of the solvent gave a crude mixture that was purified by reverse phase HPLC with a gradient of acetonitrile/water (2% to 98%) to afford ethyl 3-(2-oxo-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)propanoate (65 mg, 0.18 mmol, 58%). LCMS mz 364.0 (M+H), 386.0 (M+Na), anal HPLC>99% in purity. 1H NMR (400 MHz; CD3CN) δ7.87 (d, J=8.2 Hz, 2H); 7.81 (d, J=8.6 Hz, 2H); 7.66 (d, J=2.3 Hz, 1H); 7.63 (m, 1H); 7.26 (d, J=8.6 Hz, 1H); 4.25 (m, 2H); 3.02 (m, 2H); 2.67 (m, 4H).

Workup

  1. stirringstirring
  2. customSolvent was removed from the reaction mixture under reduced pressure
  3. additiondiluted with ethyl acetate (20 mL), and aqueous Na2SO3 (10 mL)
  4. additionadded
  5. extractionThe aqueous phase was extracted with ethyl acetate (3×20 mL)
  6. washthe combined organic phase successively washed with 2N sodium carbonate (20 mL), 30% ammonium chloride (20 mL), brine (20 mL)
  7. dry with materialdried over magnesium sulfate
  8. customEvaporation of the solvent
  9. customgave a crude mixture that
  10. customwas purified by reverse phase HPLC with a gradient of acetonitrile/water (2% to 98%)

Sources & evidence

ORD record
ord-1caa661c59e042209d3fd682a293dd76
Source dataset
uspto-grants-2014_03
Patent number
US08664379B2

Reaction notes

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