Quinoline → 3-Bromo-2-chloro-5-(trifluoromethyl)pyridine

HRID 1976060Notes

Reaction equation

HRID 1976060 reaction equation
P(Cl)(Cl)([Cl:3])=O.N1C2C(=CC=CC=2)C=CC=1.[Br:16][C:17]1[C:18](=O)[NH:19][CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:22]=1.C(=O)(O)[O-].[Na+]>O>[Br:16][C:17]1[C:18]([Cl:3])=[N:19][CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:22]=1

Participants

6

Reactant 4

HCID 7047QuinolineHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 134917753-Bromo-5-(trifluoromethyl)pyridin-2(1H)-one

Product 1

HCID 135360613-Bromo-2-chloro-5-(trifluoromethyl)pyridineYield 77.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

To phosphorous oxychloride (2.02 mL, 21.6 mmol) was added quinoline (1.34 mL, 11.2 mmol) followed by 3-bromo-5-trifluoromethyl-2(1H)-pyridone (5.0 g, 20.07 mmol). The mixture was heated at 120° C. for 3 hrs, then cooled to 100° C., whn water (10 mL) was carefully added. After cooling to room temperature, saturated sodium bicarbonate was added (100 mL) and the mixture extracted with ethyl acetate (2×100 mL). The extracts were dried (MgSO4) and concentrated, and the residue purified by silica chromatography to give the product as a liquid (4.05 g, 15.5 mmol, 75% yield).

Workup

  1. temperaturecooled to 100° C.
  2. temperatureAfter cooling to room temperature
  3. extractionthe mixture extracted with ethyl acetate (2×100 mL)
  4. dry with materialThe extracts were dried (MgSO4)
  5. concentrationconcentrated
  6. customthe residue purified by silica chromatography

Sources & evidence

ORD record
ord-631edc8691df425b8b84896b6b3881fd
Source dataset
uspto-grants-2001_05
Patent number
US06225320B1

Reaction notes

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