Dimethylformamide → 5-(Trifluoromethyl)pyridine-3-carbonitrile

HRID 2070972Notes

Reaction equation

HRID 2070972 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[CH3:12][N:13](C=O)C>CCOCC.[NH4+].[OH-].[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:9][C:8]([F:11])([F:10])[C:6]1[CH:5]=[N:4][CH:3]=[C:2]([CH:7]=1)[C:12]#[N:13]

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 111279913-Bromo-5-(trifluoromethyl)pyridine

Product 1

HCID 283061685-(Trifluoromethyl)pyridine-3-carbonitrileYield 44%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolventHCID 14923Ammonium HydroxideSolvent

Conditions

Temperature
80 °C

Procedure

3-bromo-5-(trifluoromethyl)pyridine (1.0 g, 4.42 mmol, 1 eq) was dissolved in 20 mL anhydrous DMF. The solution was degassed by bubbling through with Ar. Zn(CN)2 (0.312 g, 2.65 mmol, 0.6 eq) and Pd(PPh3)4 were added, and the resulting solution was heated to 80° C. with stirring overnight. The reaction was cooled to room temperature and diluted with Et2O, NH4OH (28%) was added with stirring and the layers were separated. The organic layer was washed with water (×3), brine (×1), and dried over Na2SO4. The inorganics were filtered off, and the reaction mixture was concentrated in vacuo. Purification via flash chromatography on silica gel yielded 0.310 g (1.95 mmol, 44% yield) of 5-(trifluoromethyl)nicotinonitrile.

Workup

  1. customThe solution was degassed
  2. customby bubbling through with Ar
  3. temperatureThe reaction was cooled to room temperature
  4. additionwas added
  5. stirringwith stirring
  6. customthe layers were separated
  7. washThe organic layer was washed with water (×3), brine (×1)
  8. dry with materialdried over Na2SO4
  9. filtrationThe inorganics were filtered off
  10. concentrationthe reaction mixture was concentrated in vacuo
  11. customPurification via flash chromatography on silica gel

Sources & evidence

ORD record
ord-d8c49f78c88d4da7a3148306b4f73ea6
Source dataset
uspto-grants-2012_10
Patent number
US08299267B2

Reaction notes

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