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

HRID 1436798Notes

Reaction equation

HRID 1436798 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 Mflz, 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-85042c42447f4ad8bfbff8c8eb15be68
Source dataset
uspto-grants-2009_11
Patent number
US07618970B2

Reaction notes

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