Water → 4-(3-Trifluoromethylphenoxy)-2-(3,5-dimethylpyrazol-1-yl)-pyrimidine

HRID 651734Notes

Reaction equation

HRID 651734 reaction equation
O.Cl[C:3](Cl)(Cl)[CH2:4][CH:5](Cl)OCC.[N+]([O-])(O)=O.[CH3:16][C:17]1[CH:21]=[C:20]([CH3:22])[N:19]([C:23]([NH2:25])=[NH:24])[N:18]=1.[F:26][C:27]([F:36])([F:35])[C:28]1[CH:29]=[C:30]([OH:34])[CH:31]=[CH:32][CH:33]=1.C(=O)([O-])[O-].[K+].[K+].ClC(Cl)=CC=O>C(COC)OC.[N+]([O-])(O)=O.CC1C=C(C)N(C(N)=N)N=1>[F:26][C:27]([F:35])([F:36])[C:28]1[CH:29]=[C:30]([CH:31]=[CH:32][CH:33]=1)[O:34][C:3]1[CH:4]=[CH:5][N:25]=[C:23]([N:19]2[C:20]([CH3:22])=[CH:21][C:17]([CH3:16])=[N:18]2)[N:24]=1

Participants

9

Reactant 6

HCID 962WaterHCID 73763-(Trifluoromethyl)phenolHCID 11430Potassium CarbonateHCID 175543,3-Dichloro-2-propenalHCID 1981863,5-Dimethyl-1H-pyrazole-1-carboxamidine mononitrateHCID 123508221,1,1,3-Tetrachloro-3-ethoxypropane

Product 1

HCID 98406254-(3-Trifluoromethylphenoxy)-2-(3,5-dimethylpyrazol-1-yl)-pyrimidineYield 65.8%

Reagents, catalysts & solvents 2

HCID 1981863,5-Dimethyl-1H-pyrazole-1-carboxamidine mononitrateCatalystHCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
90 °C

Procedure

Water (20 mmoles) is added to a solution of 1,1,1,3-tetrachloro-3-ethoxypropane (10 mmoles) in dimethoxyethane (25 ml). The mixture is stirred for 2 h at 90° C. The resulting mixture is slowly added to a mixture consisting of a 3,5-dimethylpyrazole-1-carboxamidine nitrate (10 mmoles), 3-trifluoromethylphenol (10 mmoles), potassium carbonate (60 mmoles) and dimethoxyethane (50 ml), which is stirred under reflux. When the addition of 3,3-dichloroacrolein solution is completed additional 3,5-dimethylpyrazole-1-carboxamidine nitrate (0.5 mmoles) is added. The reaction mixture is stirred for 10 hours under reflux and subsequently cooled down to ambient temperature, filtered through silica, and the organic phase is concentrated in vacuo. The residue is purified by chromatography on SiO2 (ethyl acetate) to give 2,2 g of a yellow solid. The solid was washed with petrol ether (50 ml) to yield 1,75 g (52%) of colorless crystals having a melting point of 101-102° C.

Workup

  1. additionThe resulting mixture is slowly added to a mixture
  2. stirringis stirred
  3. temperatureunder reflux
  4. additionis added
  5. stirringThe reaction mixture is stirred for 10 hours
  6. temperatureunder reflux
  7. temperaturesubsequently cooled down to ambient temperature
  8. filtrationfiltered through silica
  9. concentrationthe organic phase is concentrated in vacuo
  10. customThe residue is purified by chromatography on SiO2 (ethyl acetate)

Sources & evidence

ORD record
ord-6034720edf144f68a5a1fdc9f808c53f
Source dataset
uspto-grants-2001_08
Patent number
US06281358B1

Reaction notes

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