Sodium Carbonate → 5-fluoro-1H-indole-6-carbonitrile

HRID 1512847Notes

Reaction equation

HRID 1512847 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1I)[NH:7][CH:6]=[CH:5]2.C([O-])([O-])=O.[Na+].[Na+].[CH3:18][N:19](C)C(=O)C>[Fe-4](C#N)(C#N)(C#N)(C#N)(C#N)C#N.[K+].[K+].[K+].[K+].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[C:18]#[N:19])[NH:7][CH:6]=[CH:5]2

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 31374DimethylacetamideHCID 226127725-fluoro-6-iodo-1H-indole

Product 1

HCID 670253175-fluoro-1H-indole-6-carbonitrile

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 178511492HCID 178511492, compoundCatalyst

Procedure

To a microwave reaction vessel was added 5-fluoro-6-iodo-1H-indole (1 g), potassium ferrocyanide (1.41 g), Na2CO3 (0.80 g), PdCl2(dppf)-CH2Cl2 adduct (0.31 g) and N,N-dimethylacetamide (DMA). The reaction vessel was then sealed and heated in Biotage Initiator using initial high to 140° C. for 2 hours. After cooling the reaction, the solvent was evaporated and the residue was partitioned between water (50 mL) and ethyl acetate (50 mL). The insolubles were filtered, the organics were evaporated and the residue was chromatographed on silica gel to give the designed product 5-fluoro-1H-indole-6-carbonitrile (D151) (0.25 g). MS (ES): C9H5FN2 requires 160.0; found 161.1 (M+H+).

Workup

  1. customTo a microwave reaction vessel
  2. customThe reaction vessel was then sealed
  3. temperatureheated in Biotage Initiator
  4. customhigh to 140° C.
  5. customfor 2 hours
  6. temperatureAfter cooling
  7. customthe reaction
  8. customthe solvent was evaporated
  9. customthe residue was partitioned between water (50 mL) and ethyl acetate (50 mL)
  10. filtrationThe insolubles were filtered
  11. customthe organics were evaporated
  12. customthe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-3eea6857b8bd4441a65433e697b8a2ff
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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