Sodium hydride → 6-(Trifluoromethyl)indole

HRID 1666809Notes

Reaction equation

HRID 1666809 reaction equation
[H-].[Na+].[F:3][C:4]([F:19])([F:18])[C:5]1[CH:6]=[CH:7][CH:8]=[C:9]([NH:11][C:12]#[C:13][Si](C)(C)C)[CH:10]=1>CCO>[F:3][C:4]([F:19])([F:18])[C:5]1[CH:10]=[C:9]2[C:8]([CH:13]=[CH:12][NH:11]2)=[CH:7][CH:6]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 534238715-Trifluoromethyl-2-trimethylsilanylethynylphenylamine

Product 1

HCID 27775236-(Trifluoromethyl)indole

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

Carefully add NaH (10.83 g, 60% in oil, 270.8 mmol, 4 eq.) to EtOH (200 mL). When cool, add a solution of 5-trifluoromethyl-2-trimethylsilanylethynylphenylamine (22.3 g, 67.7 mmol) in EtOH (400 mL) with vigorous stirring. After 2 hours, heat to reflux. After 4 hours, evaporate in vacuo to remove the EtOH and dilute the residue obtained with water and extract with Et2O. Combine the organic layers and wash with brine, dry over MgSO4, filter, and evaporate to give a dark oil. Absorbed the oil onto silica gel and load onto short column of silica gel. Elute with 20% EtOAc in hexanes. Pool fractions containing the product and remove the solvent leaving a dark brown oil. Further purification of the oil by HPLC (silica column) using a gradient 1% Et2O in hexanes to 15% Et2O in hexanes. Pool fractions containing the product and remove the solvent to give the title compound as an orange solid: 1H NMR (300 MHz, d6-DMSO-d6): 6.58 (m, 1H), 7.28 (m, 1H), 7.61 (t, 1H), 7.74 (m, 2H), 11.51 (bs, 1H); MS (EI+): m/z 185 (M+).

Workup

  1. temperatureWhen cool
  2. temperatureheat to reflux
  3. waitAfter 4 hours
  4. customevaporate in vacuo
  5. customto remove the EtOH
  6. additiondilute the residue
  7. customobtained with water
  8. extractionextract with Et2O
  9. washwash with brine
  10. dry with materialdry over MgSO4
  11. filtrationfilter
  12. customevaporate
  13. customto give a dark oil
  14. customAbsorbed the oil onto silica gel and load onto short column of silica gel
  15. washElute with 20% EtOAc in hexanes
  16. additionPool fractions containing the product
  17. customremove the solvent
  18. customleaving a dark brown oil
  19. customFurther purification of the oil by HPLC (silica column)
  20. additionPool fractions containing the product
  21. customremove the solvent

Sources & evidence

ORD record
ord-66453b89c9ea409da98b27661e05e45b
Source dataset
uspto-grants-2011_10
Patent number
US08044090B2

Reaction notes

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