Dimethylformamide → 6-fluoro-3-formyl-1H-indole-7-carbonitrile

HRID 1512839Notes

Reaction equation

HRID 1512839 reaction equation
[C:1](Cl)([C:3](Cl)=O)=[O:2].CN(C=O)C.[F:12][C:13]1[C:21]([C:22]#[N:23])=[C:20]2[C:16](C=[CH:18][NH:19]2)=[CH:15][CH:14]=1>C(Cl)Cl>[F:12][C:13]1[C:21]([C:22]#[N:23])=[C:20]2[C:16]([C:3]([CH:1]=[O:2])=[CH:18][NH:19]2)=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 591461546-fluoro-1H-indole-7-carbonitrile

Product 1

HCID 591460486-fluoro-3-formyl-1H-indole-7-carbonitrileYield 98.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of (COCl)2 (2.47 g) in DCM (40 mL) at 0° C. was added a solution of DMF (3 mL) in DCM (20 mL) dropwise. Half an hour later, a solution of 6-fluoro-1H-indole-7-carbonitrile (D141) (2.6 g) in DCM (20 mL) was added. The reaction was allowed to warm to RT to form a yellow precipitate. After 5 hours the solvent was removed by evaporation, and then THF (30 mL) and 2 M aqueous NaOH (30 mL) solution were added to the residue obtained above. After stirring for about 1 h, the organic phase was separated and the aqueous phase was extracted with EtOAc (3×50 mL). The combined organic layers were dried over Na2SO4 and concentrated to afford 6-fluoro-3-formyl-1H-indole-7-carbonitrile (D142) (3.0 g) as a yellow solid.

Workup

  1. customto form a yellow precipitate
  2. customAfter 5 hours the solvent was removed by evaporation
  3. additionTHF (30 mL) and 2 M aqueous NaOH (30 mL) solution were added to the residue
  4. customobtained above
  5. customthe organic phase was separated
  6. extractionthe aqueous phase was extracted with EtOAc (3×50 mL)
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-9cf6de83f0934827911f7d3d4d1b228b
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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