Sodium Trifluoroacetate → 5-Chloro-1-methylindole

HRID 1441024Notes

Reaction equation

HRID 1441024 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:11])[C:6](I)=[CH:5]2.FC(F)(F)C([O-])=O.[Na+]>CN1CCCC1=O.O.[Cu]I>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:11])[CH:6]=[CH:5]2

Participants

6

Reactant 2

HCID 517019Sodium TrifluoroacetateHCID 153353185-chloro-2-iodo-1-methyl-1H-indole

Product 1

HCID 108558435-Chloro-1-methylindole

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 5-chloro-2-iodo-1-methylindole obtained from Example 3 (16.5 g, 56.6 mmole), sodium trifluoroacetate (76.2 g, 56.0 mmole) and copper (I) iodide (10.6 g, 56.0 mmole) in N-methylpyrrolidone is heated at 160° C. for about 8 hours, cooled to room temperature, diluted with water and filtered through diatomaceous earth. The filtrate is extracted with diethyl ether. The extracts are combined, washed with water, dried over MgSO4 and concentrated in vacuo to give a black oil residue. The residue is chromatographed using silica gel and 15:1 hexanes:ethyl acetate to give a yellow oil. The oil is chromatographed a second time using the same eluent and silica gel to give the title product as a yellow oil, 2.92 g (22% overall yield from 5-chloro-1-methylindole), identified by IR, 1HNMR, 13CNMR and 19FNMR analyses.

Workup

  1. temperaturecooled to room temperature
  2. filtrationfiltered through diatomaceous earth
  3. extractionThe filtrate is extracted with diethyl ether
  4. washwashed with water
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customto give a black oil residue
  8. customThe residue is chromatographed
  9. customethyl acetate to give a yellow oil
  10. customThe oil is chromatographed a second time
  11. customto give

Sources & evidence

ORD record
ord-1dfe47df0add4160996535198ced6c26
Source dataset
uspto-grants-1996_03
Patent number
US05502071

Reaction notes

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