Ethanol → 2-Methyl-6-nitro-1H-indole

HRID 2079913

Reaction equation

HRID 2079913 reaction equation
[H-].[Na+].[N+:3]([C:6]1[CH:7]=[CH:8][C:9]([C:13]#[C:14][CH3:15])=[C:10]([NH2:12])[CH:11]=1)([O-:5])=[O:4].ClC(OCC)=O.[O-]CC.[Na+].C(O)C>CN(C=O)C.C(OCC)(=O)C>[CH3:15][C:14]1[NH:12][C:10]2[C:9]([CH:13]=1)=[CH:8][CH:7]=[C:6]([N+:3]([O-:5])=[O:4])[CH:11]=2

Participants

8

Reactant 5

HCID 702EthanolHCID 10928Ethyl chloroformateHCID 24758Sodium hydrideHCID 2723922Sodium ethoxideHCID 671007405-Nitro-2-prop-1-ynyl-phenylamine

Product 1

HCID 6005082-Methyl-6-nitro-1H-indole

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Cool a mixture of sodium hydride (60% dispersion in oil, 0.33 g, 8.19 mmol) in anhydrous DMF to 0° C. under inert atmosphere. Add 5-nitro-2-prop-1-ynyl-phenylamine 17 (1.31 g, 7.44 mmol) in 10 mL DMF and stir 5 minutes. Add ethyl chloroformate (0.78 mL, 8.19 mmol), warm to ambient temperature, and stir 2 hours. Quench the reaction with saturated aqueous sodium bicarbonate, add ethyl acetate, and wash with saturated aqueous sodium bicarbonate followed by saturated aqueous brine. Dry the organic layer over sodium sulfate, filter, and concentrate in vacuo. Add to the residue a solution of sodium ethoxide in ethanol (0.6 M, 50 mL, 0.30 mmol) and reflux 14 hours. Cool to ambient temperature and concentrate in vacuo. Redissolve the residue in diethyl ether and wash with saturated aqueous sodium bicarbonate followed by saturated aqueous brine. Dry the organic layer over sodium sulfate, filter, concentrate in vacuo, and chromatograph the residue over silica gel, eluting with hexanes/ethyl acetate (9:1) to afford the title compound, 0.79 g (60%). LRMS (API ES−)=175.0 (M−H).

Workup

  1. temperatureCool
  2. customQuench
  3. customthe reaction with saturated aqueous sodium bicarbonate
  4. washwash with saturated aqueous sodium bicarbonate
  5. dry with materialDry the organic layer over sodium sulfate
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. temperaturereflux 14 hours
  9. concentrationconcentrate in vacuo
  10. dissolutionRedissolve the residue in diethyl ether
  11. washwash with saturated aqueous sodium bicarbonate
  12. dry with materialDry the organic layer over sodium sulfate
  13. filtrationfilter
  14. concentrationconcentrate in vacuo, and chromatograph the residue over silica gel
  15. washeluting with hexanes/ethyl acetate (9:1)

Sources & evidence

ORD record
ord-b7443fbb105549c2ac2a8095ee759b5e
Source dataset
uspto-grants-2011_04
Patent number
US07932284B2

Linked notes

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