Dimethylformamide → 4-Fluoro-1H-indole-7-carbonitrile

HRID 1512754Notes

Reaction equation

HRID 1512754 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:11])=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2.C(Cl)Cl.[CH3:15][N:16](C=O)C>[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:11][C:5]1[CH:4]=[CH:3][C:2]([C:15]#[N:16])=[C:10]2[C:6]=1[CH:7]=[CH:8][NH:9]2

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 6344DichloromethaneHCID 43429567-bromo-4-fluoro-1H-indole

Product 1

HCID 224730224-Fluoro-1H-indole-7-carbonitrile

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

To a solution of 7-bromo-4-fluoro-1H-indole (D40) (20.0 g) in DMF (250 mL) under N2 atmosphere were added Zn(CN)2 (44.0 g) and then Pd(PPh3)4 (20.0 g). The reaction mixture was heated at 120° C. overnight. After cooling, DCM (700 mL) was added to the resulting mixture. The mixture was filtered. Then DCM (1.0 L) and H2O (1.5 L) were added to the filtrate. The organic phase was separated and the aqueous phase was extracted with DCM. The combined organic layers were washed with H2O, dried over anhydrous sodium sulfate and then concentrated. The residue was purified by column chromatography on silical gel to afford 4-fluoro-1H-indole-7-carbonitrile (D41) as a white solid (11.5 g).

Workup

  1. temperatureAfter cooling
  2. filtrationThe mixture was filtered
  3. additionThen DCM (1.0 L) and H2O (1.5 L) were added to the filtrate
  4. customThe organic phase was separated
  5. extractionthe aqueous phase was extracted with DCM
  6. washThe combined organic layers were washed with H2O
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography on silical gel

Sources & evidence

ORD record
ord-362ec011333546d3801e7e290956512e
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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