Dimethylformamide → 5-fluoro-1H-indole-7-carbonitrile

HRID 1512830Notes

Reaction equation

HRID 1512830 reaction equation
Br[C:2]1[CH:3]=[C:4]([F:11])[CH:5]=[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:4]1[CH:5]=[C:6]2[C:10](=[C:2]([C:15]#[N:16])[CH:3]=1)[NH:9][CH:8]=[CH:7]2

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 6344DichloromethaneHCID 38528797-bromo-5-fluoro-1H-indole

Product 1

HCID 36962535-fluoro-1H-indole-7-carbonitrileYield 64%

Reagents, catalysts & solvents 2

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

Procedure

To a solution of 7-bromo-5-fluoro-1H-indole (D131) (15 g) in DMF (150 mL) under N2 atmosphere were added Zn(CN)2 (24.0 g) and then Pd(PPh3)4 (15.8 g), the reaction mixture was heated to 120° C. and stirred overnight. After cooling, DCM (300 mL) was added to the resulting mixture which was filtered and the filtrate was concentrated. The crude product was purified by column chromatography to afford 7 g (64% yield) of 5-fluoro-1H-indole-7-carbonitrile (D132) as a white solid. δH (CDCl3, 400 MHz): 6.51 (1H, t), 7.20 (1H, dd), 7.30 (1H, t), 7.52 (1H, dd), 8.82 (1H, br s).

Workup

  1. temperatureAfter cooling
  2. filtrationwas filtered
  3. concentrationthe filtrate was concentrated
  4. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-4dee17daa31648788046a520a7107c3a
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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