Water → 6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-2(1H)-one

HRID 1183759Notes

Reaction equation

HRID 1183759 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6][CH2:5]2.[F:13][C:14]([F:25])([F:24])[C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1.C(=O)(O)[O-].[Na+].O>CN(C)C=O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CO>[F:13][C:14]([F:25])([F:24])[C:15]1[CH:20]=[CH:19][C:18]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[NH:8][C:7](=[O:12])[CH2:6][CH2:5]3)=[CH:17][CH:16]=1

Participants

9

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 143732816-Bromo-3,4-dihydroquinolin-2(1H)-one2×

Product 1

HCID 120009366-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-2(1H)-oneYield 75%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-bromo-3,4-dihydroquinolin-2(1H)-one (2.260 g, 10.00 mmol) and 4-(trifluoromethyl)phenyl boronic acid (2.850 g, 15.00 mmol) in N,N-dimethylformamide (50 mL) was added sodium bicarbonate (3.360 g, 40.00 mmol) and water (5 mL). The reaction mixture was stirred for 5 minutes under an atmosphere of dry N2, then Pd(PPh3)4 (579 mg, 0.50 mmol) was added, and the resulting mixture was heated at 70° C. until the starting material (6-bromo-3,4-dihydroquinolin-2(1H)-one) was no longer seen by TLC. The mixture was cooled, diluted with ethyl acetate (50 mL), filtered through a layer of celite, which was washed with 10% N,N-dimethylformamide in ethyl acetate (100 mL), and the filtrate transferred to a separation funnel. The organic phase was washed with 1N sodium carbonate (100 mL), 30% ammonium chloride (100 mL), and brine (100 mL). Solvent was removed under reduced pressure to provide a yellow solid. Methanol (5.0 mL) was added, and the mixture sonicated, filtered, washed with methanol (5.0 mL), and dried under reduced pressure to afford 6-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-2(1H)-one (2.184 g, 7.5 mmol, 75%). LCMS mz 292.0 (M+H), anal HPLC ca 94% in purity, 1H NMR (400 MHz; CDCl3) δ 7.98 (s, 1H); 7.66 (m, 4H); 7.40-7.50 (m, 2H); 6.86 (d, J=9.0 Hz, 1H); 3.06 (t, J=7.6 Hz, 2H); 2.70 (t, J=7.6 Hz, 2H).

Workup

  1. temperatureThe mixture was cooled
  2. filtrationfiltered through a layer of celite, which
  3. washwas washed with 10% N,N-dimethylformamide in ethyl acetate (100 mL)
  4. customthe filtrate transferred to a separation funnel
  5. washThe organic phase was washed with 1N sodium carbonate (100 mL), 30% ammonium chloride (100 mL), and brine (100 mL)
  6. customSolvent was removed under reduced pressure
  7. customto provide a yellow solid
  8. customthe mixture sonicated
  9. filtrationfiltered
  10. washwashed with methanol (5.0 mL)
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-2cd8fa4acba246dc8e6a4c9397954592
Source dataset
uspto-grants-2014_03
Patent number
US08664379B2

Reaction notes

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