Dimethylformamide → 5,6-Difluoro-1h-indole-3-carbaldehyde

HRID 1527218Notes

Reaction equation

HRID 1527218 reaction equation
[C:1](Cl)(=[O:5])[C:2](Cl)=O.CN(C=O)C.[F:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][C:21]=1[F:22])[NH:18][CH:17]=C2>C(Cl)Cl>[F:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][C:21]=1[F:22])[NH:18][CH:17]=[C:2]2[CH:1]=[O:5]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 27787325,6-Difluoro-1H-indole

Product 1

HCID 184620795,6-Difluoro-1h-indole-3-carbaldehyde

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To an ice-cooled solution of oxalyl chloride (1.21 mL, 13.8 mmol) in CH2Cl2 (40 mL) was added a solution of DMF (2.02 mL) in CH2Cl2 (40.0 mL). The reaction was stirred for 30 min, then 5,6-difluoro-1H-indole [169674-01-5] (2.00 g, 13.1 mmol) was added in one portion. The reaction mixture was allowed to warm to RT overnight. Volatiles were evaporated, and the residue was taken up in THF (20 mL) and 20% aqueous ammonium acetate solution (20 mL). The resulting mixture was heated to reflux for 30 min. After cooling, the mixture was treated with saturated aqueous NaHCO3 solution and extracted three times with EtOAc. The combined organic layers were dried (phase separator) and evaporated in vacuo to afford the title compound as a beige solid: MS (LC/MS): 182.0 [M+H]+; tR (HPLC conditions c): 3.94 min. The material thus obtained was used in the next step without further purification.

Workup

  1. customVolatiles were evaporated
  2. temperatureThe resulting mixture was heated
  3. temperatureto reflux for 30 min
  4. temperatureAfter cooling
  5. additionthe mixture was treated with saturated aqueous NaHCO3 solution
  6. extractionextracted three times with EtOAc
  7. customThe combined organic layers were dried (phase separator)
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-b122cf80a26d42f3b77a8e4a2dbc005b
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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