N,N,N',N'-Tetramethylethylenediamine → 5-Methoxy-2-(trifluoromethyl)-1H-indole

HRID 1449630Notes

Reaction equation

HRID 1449630 reaction equation
CN(C)CCN(C)C.C([Li])CCC.C[Si](C)(C)[NH:16][C:17]1[C:18]([CH3:25])=[CH:19][C:20]([O:23][CH3:24])=[CH:21][CH:22]=1.[F:28][C:29]([F:36])([F:35])[C:30](OCC)=O>C1CCCCC1>[CH3:24][O:23][C:20]1[CH:19]=[C:18]2[C:17](=[CH:22][CH:21]=1)[NH:16][C:30]([C:29]([F:36])([F:35])[F:28])=[CH:25]2

Participants

6

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 9794Ethyl trifluoroacetateHCID 15335342N-(trimethylsilyl)-4-methoxy-o-toluidineHCID 178418339Butyllithium

Product 1

HCID 153353435-Methoxy-2-(trifluoromethyl)-1H-indoleYield 12%

Reagents, catalysts & solvents 1

HCID 8078CyclohexaneSolvent

Procedure

Tetramethylethylenediamine (TMEDA) (49 g, 0.42 mole), under nitrogen, is treated with n-butyl lithium (168 mL of 2.57 N in hexanes, 0.42 mole) at 0° C., stirred for 0.5 hour at room temperature, treated dropwise with N-(trimethylsilyl)-4-methoxy-o-toluidine (40.0 g, 0.19 mole), heated at reflux temperature for 4 hours, cooled to -78° C., diluted with dry cyclohexane, treated dropwise with ethyl trifluoroacetate (45 g, 0.23 mole), stirred at -78° C. for 0.5 hour, warmed to room temperature and quenched with saturated NH4Cl solution. The mixture is extracted with diethyl ether. The combined extracts are washed sequentially with saturated NH4Cl and brine, dried over Na2SO4 and concentrated in vacuo to give a brown oil residue. The oil is chromatographed (silica gel/10% ethyl acetate in hexanes) to give the title product as white needles, 5.0 g (12% yield), mp 60° C. (after recrystallization from pentane), identified by IR, 1HNMR, 13CNMR, 19FNMR and mass spectral analyses.

Workup

  1. temperatureheated
  2. temperatureat reflux temperature for 4 hours
  3. temperaturecooled to -78° C.
  4. stirringstirred at -78° C. for 0.5 hour
  5. temperaturewarmed to room temperature
  6. customquenched with saturated NH4Cl solution
  7. extractionThe mixture is extracted with diethyl ether
  8. washThe combined extracts are washed sequentially with saturated NH4Cl and brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated in vacuo
  11. customto give a brown oil residue
  12. customThe oil is chromatographed (silica gel/10% ethyl acetate in hexanes)
  13. customto give
  14. customthe title product as white needles, 5.0 g (12% yield), mp 60° C. (after recrystallization from pentane)

Sources & evidence

ORD record
ord-c9fe0cbd158e43e5842fc11e2352c810
Source dataset
uspto-grants-1997_02
Patent number
US05599832

Reaction notes

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