Sodium Carbonate → 4-[5-chloro-2-(1-methyl-1-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}ethoxy)phenyl]pyridine dihydrochloride

HRID 389142Notes

Reaction equation

HRID 389142 reaction equation
[N:1]1[CH:6]=[CH:5][C:4](B(O)O)=[CH:3][CH:2]=1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:17]1[CH:42]=[C:41]([Cl:43])[CH:40]=[CH:39][C:18]=1[O:19][C:20]([C:23]1[N:27]([CH3:28])[C:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[C:35]([F:38])([F:37])[F:36])=[N:25][N:24]=1)([CH3:22])[CH3:21]>C1(C)C(CCO)=CC=CC=1.O>[ClH:43].[ClH:43].[Cl:43][C:41]1[CH:42]=[CH:17][C:18]([O:19][C:20]([CH3:22])([C:23]2[N:27]([CH3:28])[C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[C:35]([F:36])([F:37])[F:38])=[N:25][N:24]=2)[CH3:21])=[C:39]([C:4]2[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=2)[CH:40]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 582438453-[1-(2-bromo-4-chlorophenoxy)-1-methylethyl]-4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazole

Product 1

HCID 866530204-[5-chloro-2-(1-methyl-1-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}ethoxy)phenyl]pyridine dihydrochlorideYield 49.6%

Reagents, catalysts & solvents 1

HCID 66602552Toluene-ethanol waterSolvent

Conditions

Temperature
110 °C

Procedure

Pyridin-4-ylboronic acid (26 mg), tetrakis triphenylphosphine palladium (10 mg) and sodium carbonate (156 mg) were added to a mixed solution of 3-[1-(2-bromo-4-chlorophenoxy)-1-methylethyl]-4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazole (100 mg) in toluene-ethanol-water (2 ml, 3:2:1), followed by stirring at 110° C. for 2 days. The reaction solution was concentrated under reduced pressure and diluted with chloroform. The organic layer was washed with water and saturated brine in this order and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by thin layer chromatography (ethyl acetate:methanol=98:2). The resulting solid was dissolved in ethyl acetate and 4M hydrogen chloride-ethyl acetate was added thereto, followed by stirring at room temperature for 2 hours. The precipitated crystal was collected by filtration and washed with ethyl acetate to obtain 4-[5-chloro-2-(1-methyl-1-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}ethoxy)phenyl]pyridine dihydrochloride (19 mg) as a white crystal.

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure
  2. additiondiluted with chloroform
  3. washThe organic layer was washed with water and saturated brine in this order
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by thin layer chromatography (ethyl acetate:methanol=98:2)
  7. dissolutionThe resulting solid was dissolved in ethyl acetate
  8. addition4M hydrogen chloride-ethyl acetate was added
  9. stirringby stirring at room temperature for 2 hours
  10. filtrationThe precipitated crystal was collected by filtration
  11. washwashed with ethyl acetate

Sources & evidence

ORD record
ord-1ba5f80a9bd247d6b57576d9a1e09fd5
Source dataset
uspto-grants-2013_02
Patent number
US08377923B2

Reaction notes

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