Quinoline → 4-Chloro-6-(trifluoromethyl)pyrimidine

HRID 1261675Notes

Reaction equation

HRID 1261675 reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1[N:8]=[CH:7][N:6]=[C:5](O)[CH:4]=1.P(Cl)(Cl)([Cl:14])=O.N1C2C(=CC=CC=2)C=CC=1>C1(C)C=CC=CC=1.O>[Cl:14][C:5]1[CH:4]=[C:3]([C:2]([F:11])([F:10])[F:1])[N:8]=[CH:7][N:6]=1

Participants

6

Reactant 3

HCID 7047QuinolineHCID 24813Phosphorus oxychlorideHCID 178516143HCID 178516143, compound

Product 1

HCID 115428814-Chloro-6-(trifluoromethyl)pyrimidineYield 21.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A solution of 6-(trifluoromethyl)pyrimidin-4-ol (5.0 g, 30.5 mmol), phosphoryl chloride (3.41 mL, 36.6 mmol), and quinoline (2.16 mL, 18.3 mmol) in toluene (50 mL) was stirred at 100° C. for 5 h. The reaction was diluted with water and extracted with ethyl acetate three times, dried with sodium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by flash column chromatography (10% EtOAc/Hexane) to yield the desired product (1.20 g, 21.6%). 1H NMR (400 MHz, CDCl3): 9.21 ppm (1H, s), 7.78 (1H, s).

Workup

  1. extractionextracted with ethyl acetate three times
  2. dry with materialdried with sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude residue was purified by flash column chromatography (10% EtOAc/Hexane)

Sources & evidence

ORD record
ord-fde2150c36874954a66e797e549dce3f
Source dataset
uspto-grants-2013_06
Patent number
US08470827B2

Reaction notes

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