Water → tert-butyl 2-(2-oxo-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)acetate

HRID 1183760Notes

Reaction equation

HRID 1183760 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.C(=O)([O-])[O-].[K+].[K+].Br[CH2:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31].O>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[CH2:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 79177tert-Butyl bromoacetateHCID 120009366-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-2(1H)-one2×

Product 1

HCID 59316619tert-butyl 2-(2-oxo-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)acetateYield 61%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-2(1H)-one (291 mg, 1.0 mmol) in anhydrous N,N-dimethylformamide (2.5 ml) was added potassium carbonate (276 mg, 2.0 mmol), and the mixture stirred at room temperature for 5 minutes in a 5 ml Personal Chemistry microwave reaction vial. To the above mixture was added tert-butyl 2-bromoacetate (390 mg, 2.0 mmol), the vial was sealed, and subjected to microwave irradiation at 120° C. for 5 min, and then at 140° C. for 40 min until most of the 6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-2(1H)-one was converted. The reaction mixture was cooled, poured into water (40 mL), extracted with ethyl acetate (2×40 mL), the combined organic phase was washed with water (40 mL), 2N sodium carbonate (10 mL), brine (40 mL), dried over sodium sulfate, and the solvent was removed under reduced pressure. The crude product was dissolved in a mixture of N,N-dimethylformamide-methanol (1 and 2 mL respectively), subjected to reverse phase HPLC with a gradient of acetonitrile/water (2% to 98%) to afford tert-butyl 2-(2-oxo-6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-1(2H)-yl)acetate (247 mg, 0.61 mmol, 61%). LCMS mz 350.0 (M−56+H), 428.0 (M+Na), anal HPLC>98% in purity, 1H NMR (400 MHz; CDCl3) δ 7.67 (m, 4H); 7.40-7.50 (m, 2H); 6.86 (d, J=8.6 Hz, 1H); 4.63 (s, 2H); 3.04 (t, J=7.4 Hz, 2H); 2.76 (t, J=7.4 Hz, 2H), 1.48 (s, 9H).

Workup

  1. customthe vial was sealed
  2. customirradiation at 120° C. for 5 min
  3. temperatureThe reaction mixture was cooled
  4. extractionextracted with ethyl acetate (2×40 mL)
  5. washthe combined organic phase was washed with water (40 mL), 2N sodium carbonate (10 mL), brine (40 mL)
  6. dry with materialdried over sodium sulfate
  7. customthe solvent was removed under reduced pressure
  8. dissolutionThe crude product was dissolved in a mixture of N,N-dimethylformamide-methanol (1 and 2 mL respectively),

Sources & evidence

ORD record
ord-911a44b1b19e4fdba197e6431453d671
Source dataset
uspto-grants-2014_03
Patent number
US08664379B2

Reaction notes

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