3-(Trifluoromethyl)phenol → 2-Cyclopropyl-4-(3-trifluoromethylphenoxy)pyrimidine

HRID 411831

Reaction equation

HRID 411831 reaction equation
Cl[C:2](Cl)=[CH:3][CH:4]=[O:5].[CH2:7]1[CH:9]([C:10]([NH2:12])=[NH:11])[CH2:8]1.Cl.[F:14][C:15]([F:24])([F:23])[C:16]1[CH:17]=[C:18](O)[CH:19]=[CH:20][CH:21]=1.C(=O)([O-])[O-].[K+].[K+].COC(OC)C>C(COC)OC>[CH:9]1([C:10]2[N:12]=[C:4]([O:5][C:20]3[CH:19]=[CH:18][CH:17]=[C:16]([C:15]([F:24])([F:23])[F:14])[CH:21]=3)[CH:3]=[CH:2][N:11]=2)[CH2:8][CH2:7]1

Participants

7

Reactant 5

HCID 73763-(Trifluoromethyl)phenolHCID 107951,1-DimethoxyethaneHCID 11430Potassium CarbonateHCID 175543,3-Dichloro-2-propenal2×HCID 2781916Cyclopropanecarboximidamide hydrochloride2×

Product 1

HCID 98604972-Cyclopropyl-4-(3-trifluoromethylphenoxy)pyrimidineYield 75%

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 cyclopropylcarbamidine hydrochloride (10 mmoles), 3-trifluoromethylphenol (11 mmoles), potassium carbonate (40 rnmoles) and dimethyoxyethane (40 ml), which is stirred under reflux. When the addition of 3,3-dichloroacrolein is completed additional cyclopropylcarbamidine hydrochloride (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 2.1 g (75%) of the pure product having as a colorless liquid; 1H NMR (CDC13); δ=2.10 ppm (m, N═C(═N)═CH).

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-1ec957835fbf4ea59e1c911d33f439c8
Source dataset
uspto-grants-2003_05
Patent number
US06559307B2

Linked notes

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