Dimethylformamide → 6-Fluoro-1-methyl-1H-indole-3-carbaldehyde

HRID 1372759Notes

Reaction equation

HRID 1372759 reaction equation
P(Cl)(Cl)(Cl)=O.[F:6][C:7]1[CH:15]=[C:14]2[C:10]([CH:11]=[CH:12][N:13]2[CH3:16])=[CH:9][CH:8]=1.[OH-].[Na+].CN([CH:22]=[O:23])C>>[F:6][C:7]1[CH:15]=[C:14]2[C:10]([C:11]([CH:22]=[O:23])=[CH:12][N:13]2[CH3:16])=[CH:9][CH:8]=1

Participants

5

Reactant 4

HCID 6228Dimethylformamide2×HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 179553176-Fluoro-1-methyl-1h-indole

Product 1

HCID 64981976-Fluoro-1-methyl-1H-indole-3-carbaldehydeYield 52%

Procedure

Phosphoryl chloride (5.87 ml, 63.0 mmol) was added in portions while stirring DMF (45 ml) at 0° C. After stirring at the same temperature for 20 minutes, the reaction mixture was added with a solution of 6-fluoro-1-methylindole (6.71 g, 45.0 mmol) in DMF (45 ml) at 0° C. The reaction mixture was stirred for further 0.5 hour. Ice water and 1N NaOH were added to the reaction mixture to neutralize the same, followed by extraction with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from ethyl acetate eluate fractions, 6-fluoro-1-methylindole-3-carbaldehyde (4.18 g, 52%) was obtained as a colorless solid.

Workup

  1. stirringThe reaction mixture was stirred for further 0.5 hour
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationdistilled under reduced pressure
  6. customto remove the solvent
  7. customThe residue was purified by chromatography on a silica gel column, whereby from ethyl acetate eluate fractions

Sources & evidence

ORD record
ord-f178ab5909944b918151a74a07a7cff8
Source dataset
uspto-grants-2007_01
Patent number
US07157487B2

Reaction notes

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