Acetophenone → 7-Chloro-4-methyl-2-phenylquinoline

HRID 422722Notes

Reaction equation

HRID 422722 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)(=O)[CH3:2].[NH2:10][C:11]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=1[C:18](=O)[CH3:19].C(=O)([O-])[O-]>C(Cl)Cl>[Cl:17][C:15]1[CH:16]=[C:11]2[C:12]([C:18]([CH3:19])=[CH:2][C:1]([C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=3)=[N:10]2)=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 7410AcetophenoneHCID 19660Carbonate IonHCID 135747171-(2-Amino-4-chlorophenyl)ethanone

Product 1

HCID 576810187-Chloro-4-methyl-2-phenylquinoline

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

Acetophenone (0.66 mL, 5.69 mmol) was added to 1-(2-amino-4-chlorophenyl)ethanone (0.868 g, 5.69 mmol) and [Hbim]BF4 (1.50 g, 7.08 mmol) under Ar. The reaction mixture was heated at 100° C. for 57 h then cooled to rt and partitioned between EtOAc and H2O. The aq layer was extracted with EtOAc. The combined organics were dried (Na2SO4) and concentrated under reduced pressure. Purification by flash chromatography on SiO2 (70 g, EtOAc in hexanes 0:100→1:40→1:30) afforded a lightly colored oil. The material was dissolved in DCM (100 mL) and stirred with PS-Ts-NHNH2 (2.07 g, 2.87 mmol/g, 5.94 mmol) for 2.5 d at rt and then with MP-carbonate (˜0.25 g, 2.74 mmol/g, 0.68 mmol) for 4 h. The resins were removed by filtration through Celite. The residue and Celite were rinsed with DCM multiple times. The filtrate was concentrated under reduced pressure to provide the title compound as a light yellow oil; 1H NMR (400 MHz, CDCl3) δ 8.18-8.12 (m, 3H), 7.92 (d, J=8.4 Hz, 1H), 7.71 (d, J=0.8 Hz, 1H), 7.54-7.46 (m, 4H), 2.75 (s, 3H); MS (ES+): m/z 254.24 (35) [MH+]; HPLC: tR=3.82 min (OpenLynx, nonpolar—5 min).

Workup

  1. temperaturethen cooled to rt
  2. custompartitioned between EtOAc and H2O
  3. extractionThe aq layer was extracted with EtOAc
  4. dry with materialThe combined organics were dried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash chromatography on SiO2 (70 g, EtOAc in hexanes 0:100→1:40→1:30)
  7. customafforded a lightly colored oil
  8. customThe resins were removed by filtration through Celite
  9. washThe residue and Celite were rinsed with DCM multiple times
  10. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-ba52020d60be4dd597cc228bb2ecf060
Source dataset
uspto-grants-2012_01
Patent number
US08101613B2

Reaction notes

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