Dimethylformamide → 4-[1-(4-Trifluoromethoxyphenyl)-1H-[1,2,4]triazol-3-yl]-benzonitrile

HRID 62065

Reaction equation

HRID 62065 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[CH:11][N:10]([C:13]3[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=3)[N:9]=2)=[CH:4][CH:3]=1.[CH3:24][N:25](C)C=O>C(OCC)(=O)C.[C-]#N.[Zn+2].[C-]#N.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:21][C:20]([F:23])([F:22])[O:19][C:16]1[CH:17]=[CH:18][C:13]([N:10]2[CH:11]=[N:12][C:8]([C:5]3[CH:6]=[CH:7][C:2]([C:24]#[N:25])=[CH:3][CH:4]=3)=[N:9]2)=[CH:14][CH:15]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 904040773-(4-bromophenyl)-1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazole

Product 1

HCID 669571074-[1-(4-Trifluoromethoxyphenyl)-1H-[1,2,4]triazol-3-yl]-benzonitrileYield 94%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

In a 250 mL flask, 3-(4-bromophenyl)-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (4.00 g, 10.4 mmol) was dissolved in N,N-dimethylformamide (30 mL) under nitrogen atmosphere. Zinc cyanide (1.46 g, 12.4 mmol) and tetrakis(triphenylphosphine) palladium(0) (0.601 g, 0.0500 mmol) were added and the reaction mixture was heated to 110° C. for 16 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and washed with water. The aqueous layer was further extracted with ethyl acetate. The combined organics were washed with water and brine, dried over magnesium sulfate and concentrated. Purification by flash column chromatography eluting with 30% ethyl acetate/hexanes gave the title compound as off-white solid (3.40 g, 94%): mp 172-176° C.; 1H NMR (400 MHz, CDCl3): δ 8.60 (s, 1H), 8.31 (d, J=8.8 Hz, 2H), 7.81 (d, J=8.8 Hz, 2H), 7.77 (d, J=8.8 Hz, 2H), 7.41 (d, J=8.8 Hz, 2H); ES+API m/z 331 ([M+H]+).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with water
  3. extractionThe aqueous layer was further extracted with ethyl acetate
  4. washThe combined organics were washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customPurification by flash column chromatography
  8. washeluting with 30% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-6923f5cd857b4c6c972bc13a2d4e7a77
Source dataset
uspto-grants-2016_09
Patent number
US09445594B2

Linked notes

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