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

HRID 623962Notes

Reaction equation

HRID 623962 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=O)[C:6]([O:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)=[C:5]2[C:21]([F:24])([F:23])[F:22].P(Cl)(Cl)([Cl:27])=O.C(N(C(C)C)CC)(C)C>>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([Cl:27])[C:6]([O:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)=[C:5]2[C:21]([F:24])([F:23])[F:22]

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 867154486-bromo-3-(4-chlorophenoxy)-4-(trifluoromethyl)quinolin-2(1H)-one2×

Product 1

HCID 867154476-Bromo-2-chloro-3-(4-chlorophenoxy)-4-(trifluoromethyl)quinoline

Conditions

Temperature
120 °C

Procedure

To a suspension of 6-bromo-3-(4-chlorophenoxy)-4-(trifluoromethyl)quinolin-2(1H)-one (1.08 g, 2.58 mmol, Intermediate 7, step c) in phosphoryl trichloride (7.2 mL, 77.3 mmol) was added diisopropylethylamine (1.33 mL, 7.74 mmol). The resulting mixture was heated at 120° C. for 8 hours. The solution was concentrated in vacuo at room temperature and the resulting residue was cooled to 0° C. with an ice bath. To the cold residue was added ice in small portions to quench excess phosphoryl trichloride. After cessation of bubbling, the solid suspension was diluted with dichloromethane. The organic phase was separated out, dried (MgSO4), filtered and concentrated to yield the title compound.

Workup

  1. concentrationThe solution was concentrated in vacuo at room temperature
  2. temperaturethe resulting residue was cooled to 0° C. with an ice bath
  3. additionTo the cold residue was added ice in small portions
  4. customto quench excess phosphoryl trichloride
  5. customAfter cessation of bubbling
  6. additionthe solid suspension was diluted with dichloromethane
  7. customThe organic phase was separated out
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-e19ffcb028144e6ca7ee9e4a144836dc
Source dataset
uspto-grants-2016_04
Patent number
US09303015B2

Reaction notes

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