Diethyl Ether → HCID 66730744, compound

HRID 1027994Notes

Reaction equation

HRID 1027994 reaction equation
[F:1][C:2]1[C:8]([CH3:9])=[CH:7][C:5]([NH2:6])=[C:4]([C:10]#[C:11][Si:12]([CH3:15])([CH3:14])[CH3:13])[CH:3]=1.C(OCC)C>CN(C=O)C.[Cu]I>[F:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:7][C:8]=1[CH3:9])[NH:6][C:11]([Si:12]([CH3:13])([CH3:15])[CH3:14])=[CH:10]2.[F:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:7][C:8]=1[CH3:9])[NH:6][CH:11]=[CH:10]2

Participants

6

Reactant 2

HCID 3283Diethyl EtherHCID 66730565HCID 66730565, compound

Product 2

HCID 247292425-Fluoro-6-methyl-1H-indoleHCID 66730744HCID 66730744, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-fluoro-5-methyl-2-((trimethylsilyl)ethynyl)aniline (plus ca. 10% of the undesired isomer) (10.3 g, 46.6 mmol) and copper(I) iodide (17.75 g, 93.2 mmol) in DMF (200 mL) was stirred at 100° C. for 4 hours. The mixture was then treated with ethyl ether (300 mL) and filtered. The filtrate was washed with water (200 mL) and extracted with ether. The organics were combined and washed with water, brine, and dried over Na2SO4 and concentrated. The residue was purified by flash chromatography with 5-35% ethyl acetate in hexane to give 1.9 g 5-fluoro-6-methyl-2-(trimethylsilyl)-1H-indole containing ˜10% of the undesired isomer, 5-fluoro-4-methyl-2-(trimethylsilyl)-1H-indole plus desilylated product, 5-fluoro-6-methyl-1H-indole (2.8 g) with ˜10% of the undesired isomer, 5-fluoro-4-methyl-1H-indole. Silylated material, 5-fluoro-6-methyl-2-(trimethylsilyl)-1H-indole containing ˜10% of the undesired isomer, was re-dissolved in methanol (20 mL) and stirred with potassium carbonate overnight, filtered and concentrated. All desilylated material was combined (3.7 g) and recrystallized from CH2Cl2 and hexane to provide 5-fluoro-6-methyl-1H-indole (1.9 g).

Workup

  1. filtrationfiltered
  2. washThe filtrate was washed with water (200 mL)
  3. extractionextracted with ether
  4. washwashed with water, brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography with 5-35% ethyl acetate in hexane

Sources & evidence

ORD record
ord-cad966a2d4a6479b91e68497796d75b0
Source dataset
uspto-grants-2014_05
Patent number
US08735414B2

Reaction notes

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