Dimethylformamide → 6-Bromo-2-chloro-3-phenylquinoline

HRID 1478514Notes

Reaction equation

HRID 1478514 reaction equation
CN(C)C=O.P(Cl)(Cl)([Cl:8])=O.[Br:11][C:12]1[CH:17]=CC(NC(=O)CC2C=CC=CC=2)=C[CH:13]=1.Cl[C:29]1[CH:30]=[C:31]([C:35]([C:37]2C=[CH:41][N:40]=[C:39]([C:43](F)(F)F)[CH:38]=2)=O)[CH:32]=[CH:33][CH:34]=1>>[Br:11][C:12]1[CH:17]=[C:38]2[C:39](=[CH:43][CH:13]=1)[N:40]=[C:41]([Cl:8])[C:35]([C:31]1[CH:30]=[CH:29][CH:34]=[CH:33][CH:32]=1)=[CH:37]2

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 344475N-(4-bromophenyl)-2-phenylacetamideHCID 118005555(3-Chlorophenyl)(2-(trifluoromethyl)pyridin-4-yl)methanone

Product 1

HCID 132001916-Bromo-2-chloro-3-phenylquinoline

Conditions

Temperature
80 °C

Procedure

Into a 50-mL round-bottom flask were placed N,N-dimethylformamide (2.15 g, 29.45 mmol) and phosphoryl trichloride (20.3 g, 132.7 mmol) and the mixture was cooled to 0° C. Then, N-(4-bromophenyl)-2-phenylacetamide (5.7 g, 17.87 mmol, Intermediate 23: step a) was added in portions. The resulting solution was heated at 80° C. for 5 hours, then concentrated under vacuum, followed by dilution with 50 mL of H2O, and then extraction with 3×50 mL of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by FCC (1:10 EtOAc/petroleum ether) to afford the title compound as a yellow solid.

Workup

  1. customInto a 50-mL round-bottom flask were placed
  2. concentrationconcentrated under vacuum
  3. extractionextraction with 3×50 mL of ethyl acetate
  4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by FCC (1:10 EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-81595b2cbce14867b75e8f5a746b1f05
Source dataset
uspto-grants-2016_08
Patent number
US09403816B2

Reaction notes

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