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

HRID 651732Notes

Reaction equation

HRID 651732 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+]>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

6

Reactant 4

HCID 73763-(Trifluoromethyl)phenolHCID 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-DimethoxyethaneSolvent2×

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 mmoles) and dimethoxyethane (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 (CDCl3); 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-eb62fbd493b848b18cfae23ba83a32bb
Source dataset
uspto-grants-2001_08
Patent number
US06281358B1

Reaction notes

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