Potassium Hydroxide → 3-(1-Methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-5-carboxylic acid

HRID 725964Notes

Reaction equation

HRID 725964 reaction equation
[OH-].[K+].[NH:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([OH:14])=[O:13])=[CH:9][CH:10]=2)[CH:5]=[CH:4]1.[CH3:15][N:16]1[CH2:21][CH2:20][C:19](=O)[CH2:18][CH2:17]1>CO>[C:12]([C:8]1[CH:7]=[C:6]2[C:11](=[CH:10][CH:9]=1)[NH:3][CH:4]=[C:5]2[C:19]1[CH2:20][CH2:21][N:16]([CH3:15])[CH2:17][CH:18]=1)([OH:14])=[O:13]

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 740491-Methyl-4-piperidoneHCID 742801H-Indole-5-Carboxylic Acid

Product 1

HCID 190229843-(1-Methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-5-carboxylic acidYield 71%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 5.8 gm (90 mMol) potassium hydroxide in 50 mL methanol were added 4.83 gm (30 mMol) indole 5-carboxylic acid followed by 7.4 mL (60 mMol) 1-methyl-4-piperidone and the resulting solution was heated at reflux for 18 hours. The reaction mixture was then concentrated under reduced pressure and the resulting oil dissolved in 200 mL water. The solution was gradually neutralized by addition of 18 mL 5N hydrochloric acid. The precipitate which formed was isolated by filtration and washed with water to provide 6.09 gm after drying. This solid was dissolved in 100 mL 0.5N sodium hydroxide, filtered and the filtrate treated with 50 mL 1N hydrochloric acid. The solid which formed was filtered and dried under reduced pressure to provide 5.46 gm (71%) of the title compound.

Workup

  1. temperaturethe resulting solution was heated
  2. temperatureat reflux for 18 hours
  3. concentrationThe reaction mixture was then concentrated under reduced pressure
  4. dissolutionthe resulting oil dissolved in 200 mL water
  5. additionThe solution was gradually neutralized by addition of 18 mL 5N hydrochloric acid
  6. customThe precipitate which formed
  7. customwas isolated by filtration
  8. washwashed with water
  9. customto provide 6.09 gm
  10. customafter drying
  11. dissolutionThis solid was dissolved in 100 mL 0.5N sodium hydroxide
  12. filtrationfiltered
  13. additionthe filtrate treated with 50 mL 1N hydrochloric acid
  14. customThe solid which formed
  15. filtrationwas filtered
  16. customdried under reduced pressure

Sources & evidence

ORD record
ord-bb479d92b6534b93bcd1ba4c857567e4
Source dataset
uspto-grants-1998_01
Patent number
US05708008

Reaction notes

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