2-Ethynyl-4,6-difluoroaniline → 5,7-difluoro-1H-indole

HRID 923687Notes

Reaction equation

HRID 923687 reaction equation
[C:1]([C:3]1[CH:9]=[C:8]([F:10])[CH:7]=[C:6]([F:11])[C:4]=1[NH2:5])#[CH:2]>C(O)C.O.O.[Au](Cl)(Cl)Cl.[Na]>[F:10][C:8]1[CH:9]=[C:3]2[C:4](=[C:6]([F:11])[CH:7]=1)[NH:5][CH:2]=[CH:1]2

Participants

4

Reactant 1

HCID 215781382-Ethynyl-4,6-difluoroaniline

Product 1

HCID 27787305,7-difluoro-1H-indoleYield 85%

Reagents, catalysts & solvents 2

HCID 131734998Sodium gold(III) chloride dihydrateCatalystHCID 702EthanolSolvent

Procedure

The impure 2-ethynyl-4,6-difluoroaniline (4.2 g, 19 mmol) from the previous example was dissolved in ethanol (75 mL), treated with sodium gold(III) chloride dihydrate (310 mg, 0.77 mmol) and stirred for 3 h under an atmosphere of nitrogen. The mixture was concentrated, taken up in ethyl acetate, washed with water, washed with sat. NaCl, dried over sodium sulfate (Na2SO4) and evaporated. Purification by flash chromatography (SiO2, 100-200 mesh; eluting with 0-15% EtOAc in hexanes containing 2% acetic acid) provided of the title product (2.0 g, ca 85% purity): 1H NMR (400 MHz, CDCl3) δ 8.32 (s, 1H), 7.26 (dd, J=4.8, 2.0 Hz, 1H), 7.09 (dd, J=9.1, 2.2 Hz, 1H), 6.74 (ddd, J=11.2, 9.3, 2.0 Hz, 1H), 6.55 (td, J=3.3, 2.2 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ −122.11, −131.96. EIMS m/z 153.

Workup

  1. concentrationThe mixture was concentrated
  2. washwashed with water
  3. washwashed with sat. NaCl
  4. dry with materialdried over sodium sulfate (Na2SO4)
  5. customevaporated
  6. customPurification
  7. washby flash chromatography (SiO2, 100-200 mesh; eluting with 0-15% EtOAc in hexanes containing 2% acetic acid)

Sources & evidence

ORD record
ord-f11681aed86540929087e232986d94d9
Source dataset
uspto-grants-2016_03
Patent number
US09278985B2

Reaction notes

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