Ethyl Acetate → 5-Chloro-1-methyl-3,4-dihydroquinolin-2(1H)-one

HRID 1471678Notes

Reaction equation

HRID 1471678 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][CH2:10][C:11]([NH:13][CH3:14])=[O:12].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>C1(C)C=CC=CC=1.O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]2[C:3]=1[CH2:9][CH2:10][C:11](=[O:12])[N:13]2[CH3:14]

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 679825833-(2-bromo-6-chlorophenyl)-N-methylpropanamide

Product 1

HCID 679851285-Chloro-1-methyl-3,4-dihydroquinolin-2(1H)-one

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Procedure

3-(2-Bromo-6-chlorophenyl)-N-methylpropanamide (Example 1g), 2.98 g, 10.8 mmol), palladium acetate (0.12 g, 0.54 mmol), Pd2(dba)3 (0.020 g, 0.02 mmol), racemic 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.671 g, 1.08 mmol) and cesium carbonate (4.92 g, 15.1 mmol) in toluene (30 mL) and 1,4-dioxane (45 mL) were heated to +95° C. under argon for 6 h. The mixture was allowed to cool to rt. 100 mL of ethyl acetate was added and the mixture was filtered through a pad of Celite. The filtrate was collected and the solvent was removed by rotary evaporation. The crude product was added to a silica gel column and was eluted with 0-2% methanol in dichloromethane. The collected fractions were combined and the solvent was removed by rotary evaporation to give the title compound. Yield: 1.50 g, 71%. 1H NMR (500 MHz, CDCl3) δ ppm 2.66 (dd, 2H) 3.02-3.09 (m, 2H) 3.36 (s, 3H) 6.91 (d, 1H) 7.08-7.12 (m, 1H) 7.17-7.22 (m, 1H). MS m/z 196.6 [M+H]+

Workup

  1. filtrationthe mixture was filtered through a pad of Celite
  2. customThe filtrate was collected
  3. customthe solvent was removed by rotary evaporation
  4. additionThe crude product was added to a silica gel column
  5. washwas eluted with 0-2% methanol in dichloromethane
  6. customthe solvent was removed by rotary evaporation

Sources & evidence

ORD record
ord-07ff5e1181de46c9a0c9617d888bf755
Source dataset
uspto-grants-2015_04
Patent number
US09012457B2

Reaction notes

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