3-(Trifluoromethyl)phenol → 4-(3-Trifluoromethylphenoxy)-2-(4-fluorophenyl)pyrimidine

HRID 411830

Reaction equation

HRID 411830 reaction equation
Cl[C:2](Cl)=[CH:3][CH:4]=O.C(O)(=O)C.[F:11][C:12]1[CH:20]=[CH:19][C:15]([C:16]([NH2:18])=[NH:17])=[CH:14][CH:13]=1.[F:21][C:22]([F:31])([F:30])[C:23]1[CH:24]=[C:25]([OH:29])[CH:26]=[CH:27][CH:28]=1.C(=O)([O-])[O-].[K+].[K+]>C(COC)OC>[F:21][C:22]([F:30])([F:31])[C:23]1[CH:24]=[C:25]([CH:26]=[CH:27][CH:28]=1)[O:29][C:2]1[CH:3]=[CH:4][N:18]=[C:16]([C:15]2[CH:19]=[CH:20][C:12]([F:11])=[CH:13][CH:14]=2)[N:17]=1

Participants

6

Reactant 4

HCID 73763-(Trifluoromethyl)phenolHCID 11430Potassium CarbonateHCID 175543,3-Dichloro-2-propenal2×HCID 447849914-Fluorobenzamidine acetate2×

Product 1

HCID 98624974-(3-Trifluoromethylphenoxy)-2-(4-fluorophenyl)pyrimidineYield 75.4%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

3,3-Dichloroacrolein (10 mmoles) diluted with dimethoxyethane (35 ml), is slowly added to a mixture consisting of a 4-fluorobenzamidine acetate (10 mmoles), 3-trifluoromethylphenol (11 mmoles), potassium carbonate (40 mmoles) nd dimethoxyethane (40 ml), which is stirred under reflux. When the addition of 3,3-dichloroacrolein is completed additional 4-fluorobenzamidine acetate (1 mmoles) is added. The reaction mixture is stirred for 3 hours under reflux and subsequently cooled down to ambient temperature over night and filtered through silica. The organic phase is concentrated in vacuo. The residue was purified by chromatography on Al2O3 (petrol ethers/ethyl acetate: 20/1) to yield 2.52 g (75%) of the pure product having a melting point of 52° C.

Workup

  1. additionis slowly added to a mixture
  2. temperatureunder reflux
  3. additionis added
  4. stirringThe reaction mixture is stirred for 3 hours
  5. temperatureunder reflux
  6. filtrationfiltered through silica
  7. concentrationThe organic phase is concentrated in vacuo
  8. customThe residue was purified by chromatography on Al2O3 (petrol ethers/ethyl acetate: 20/1)

Sources & evidence

ORD record
ord-e7c4df2732b2437d9a887a4aae508376
Source dataset
uspto-grants-2003_05
Patent number
US06559307B2

Linked notes

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