Water → 5-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidin-1-yl]-2-(1H-1,2,4-triazol-1-yl)benzonitrile

HRID 1930525Notes

Reaction equation

HRID 1930525 reaction equation
[NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.[H-].[Na+].[Cl:8][C:9]1[CH:10]=[C:11]([C:16]2([C:30]([F:33])([F:32])[F:31])[CH2:20][CH2:19][N:18]([C:21]3[CH:22]=[CH:23][C:24](F)=[C:25]([CH:28]=3)[C:26]#[N:27])[CH2:17]2)[CH:12]=[C:13]([Cl:15])[CH:14]=1.O>CN(C=O)C>[Cl:8][C:9]1[CH:10]=[C:11]([C:16]2([C:30]([F:32])([F:33])[F:31])[CH2:20][CH2:19][N:18]([C:21]3[CH:22]=[CH:23][C:24]([N:1]4[CH:5]=[N:4][CH:3]=[N:2]4)=[C:25]([CH:28]=3)[C:26]#[N:27])[CH2:17]2)[CH:12]=[C:13]([Cl:15])[CH:14]=1

Participants

6

Reactant 4

HCID 962WaterHCID 92571H-1,2,4-TriazoleHCID 24758Sodium hydrideHCID 582188895-[3-(3,5-Dichlorophenyl)-3-(trifluoromethyl)pyrrolidin-1-yl]2-fluorobenzonitrile

Product 1

HCID 582188915-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidin-1-yl]-2-(1H-1,2,4-triazol-1-yl)benzonitrileYield 53.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To the solution of 1H-1,2,4-triazole (0.06 g) in DMF was added sodium hydride (0.04 g) while cooling with ice, and the mixture was warmed to room temperature and then stirred for 0.5 hr. To this solution was added the solution of 5-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidin-1-yl]2-fluorobenzonitrile (0.30 g) in DMF, and the mixture was heated to reflux for 6 hours. The mixture was cooled to room temperature and then poured into water, which was then extracted twice with ethyl acetate. The organic layer was combined, which was then washed with water and dried over anhydrous magnesium sulfate. After the drying agent was filtered off, the solvent was distilled away under the reduced pressure, and the residue was then purified by silica gel chromatography to yield 5-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidin-1-yl]-2-(1H-1,2,4-triazol-1-yl)benzonitrile (0.18 g). 1H-NMR (DMSO-d6) δ: 2.62-2.73 (1H, m), 2.95-3.03 (1H, m), 3.49-3.55 (2H, m), 3.90 (1H, d), 4.31 (1H, d), 7.09 (1H, dd), 7.29 (1H, d), 7.61 (1H, d), 7.68 (2H, d), 7.71 (1H, t), 8.26 (1H, s), 8.98 (1H, s)

Workup

  1. temperaturewhile cooling with ice
  2. temperaturethe mixture was heated
  3. temperatureto reflux for 6 hours
  4. temperatureThe mixture was cooled to room temperature
  5. extractionwas then extracted twice with ethyl acetate
  6. washwhich was then washed with water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationAfter the drying agent was filtered off
  9. distillationthe solvent was distilled away under the reduced pressure
  10. customthe residue was then purified by silica gel chromatography

Sources & evidence

ORD record
ord-7ee11f77817f4cdeaad5afb037a08165
Source dataset
uspto-grants-2012_05
Patent number
US08188122B2

Reaction notes

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