Potassium Hydroxide → 5-Bromo-7-methyl-1H-indole

HRID 2355952Notes

Reaction equation

HRID 2355952 reaction equation
C(OC([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([Br:15])=[CH:10][C:9]=2[CH3:16])=O)C.[OH-].[K+]>O.C(O)C>[Br:15][C:11]1[CH:12]=[C:13]2[C:8](=[C:9]([CH3:16])[CH:10]=1)[NH:7][CH:6]=[CH:14]2

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 4715166HCID 4715166, compound

Product 1

HCID 211022005-Bromo-7-methyl-1H-indole

Reagents, catalysts & solvents 1

HCID 19096565Water ethanolSolvent

Procedure

5-Bromo-7-methyl-1H-indole-2-carboxylic acid ethyl ester (5.3 g, 18.7 mmol) was added to a potassium hydroxide solution in 1:1 water/ethanol mixture (20 mL) and heated at reflux for 12 h. After cooling to room temperature, the solvents were removed in vacuo and the resultant residue transferred to a 6N hydrochloric acid solution (20 mL). The white precipitate that formed was filtered, washed severally with water, and dried for several hours. The crude solid was dissolved in quinoline (14 mL) and heated at reflux for 4 h. After cooling to room temperature, the crude mixture was poured into a mixture of ice water (100 mL) and concentrated hydrochloric acid (16 mL), extracted with ethyl acetate (2×), brine (2×), dried over sodium sulfate, and concentrated. Attempts to recrystallize the desired product from isopropanol resulted in significant decomposition. The title compound was obtained by flash chromatography on silica get to afford 1.5 g (38%, 2 steps). LC/MS: tR=1.72 min, 210.05 (MH)+.

Workup

  1. temperatureheated
  2. temperatureat reflux for 12 h
  3. customthe solvents were removed in vacuo
  4. customThe white precipitate that formed
  5. filtrationwas filtered
  6. washwashed severally with water
  7. customdried for several hours
  8. dissolutionThe crude solid was dissolved in quinoline (14 mL)
  9. temperatureheated
  10. temperatureat reflux for 4 h
  11. temperatureAfter cooling to room temperature
  12. additionthe crude mixture was poured into a mixture of ice water (100 mL) and concentrated hydrochloric acid (16 mL)
  13. extractionextracted with ethyl acetate (2×), brine (2×)
  14. dry with materialdried over sodium sulfate
  15. concentrationconcentrated
  16. customto recrystallize the desired product from isopropanol
  17. customresulted in significant decomposition

Sources & evidence

ORD record
ord-f78a91d9ff424740a3e00be4fe6a52b6
Source dataset
uspto-grants-2010_07
Patent number
US07754732B2

Reaction notes

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