Dimethylformamide → 3-Amino-6-(trifluoromethyl)picolinonitrile

HRID 1016191Notes

Reaction equation

HRID 1016191 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:9]([F:12])([F:11])[F:10])=[N:6][C:7]=1I.[CH3:13][N:14](C=O)C>[C-]#N.[Zn+2].[C-]#N.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>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:9]([F:12])([F:11])[F:10])=[N:6][C:7]=1[C:13]#[N:14]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 534254792-Iodo-6-(trifluoromethyl)pyridin-3-amine

Product 1

HCID 573645173-Amino-6-(trifluoromethyl)picolinonitrileYield 86.31%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

12.5 g (0.434 mol, 1 eq) of 5-amino-6-iodo-2-(trifluoromethyl)pyridine was dissolved in 125 mL of dry DMF and degasified with nitrogen for 5 min. 6.1 g (0.519 mol, 1.2 eq) of zinc cyanide and 5 g (0.1 eq) of Pd(PPh3)4 were added and heated at 100° C. for over night. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with brine and concentrated. The crude product obtained was purified by 60-120 silica gel using 15% of ethyl acetate in pet ether to get 7 g (86.31%) of pale yellow solid. 1H NMR (CDCl3, 400 MHz): 4.85 (2H, bs), 7.25 (1H, d), 7.62 (1H, d). MS 188 (M+H)+.

Workup

  1. customThe reaction mixture was quenched with water
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. concentrationconcentrated
  5. customThe crude product obtained
  6. customwas purified by 60-120 silica gel using 15% of ethyl acetate in pet ether

Sources & evidence

ORD record
ord-9aac442e773a4c3ba7ea6a548f044550
Source dataset
uspto-grants-2011_07
Patent number
US07985861B2

Reaction notes

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