Phosphorus oxychloride → 6-Bromo-4-chloro-3-phenyl-2-(trifluoromethyl)quinoline

HRID 1478505Notes

Reaction equation

HRID 1478505 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]([F:15])([F:14])[F:13])[C:6]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[C:5]2O.P(Cl)(Cl)([Cl:25])=O>>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]([F:15])([F:14])[F:13])[C:6]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[C:5]2[Cl:25]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178515323HCID 178515323, compound

Product 1

HCID 867160766-Bromo-4-chloro-3-phenyl-2-(trifluoromethyl)quinoline

Procedure

A solution of 6-bromo-3-phenyl-2-(trifluoromethyl)quinolin-4-ol (8.29 g, 22.5 mmol, Intermediate 19: step a) in phosphoryl trichloride (25 mL, 269 mmol) was heated at 110° C. for 2 hours, and concentrated in vacuo. Dichloromethane and ice-water were added, and the mixture was basified at 4° C. with concentrated NH4OH until pH˜10. The organic layer was separated and the aqueous layer was extracted with CH2Cl2. The combined organic phases were dried (Na2SO4), concentrated, and purified by flash column chromatography (120 g silica gel column, 2-9% EtOAc in heptanes) to afford the title compound as a light yellow solid.

Workup

  1. concentrationconcentrated in vacuo
  2. additionDichloromethane and ice-water were added
  3. customwas basified at 4° C. with concentrated NH4OH until pH˜10
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with CH2Cl2
  6. dry with materialThe combined organic phases were dried (Na2SO4)
  7. concentrationconcentrated
  8. custompurified by flash column chromatography (120 g silica gel column, 2-9% EtOAc in heptanes)

Sources & evidence

ORD record
ord-9c75719b4e844599a963827e6069f165
Source dataset
uspto-grants-2016_08
Patent number
US09403816B2

Reaction notes

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