5-methoxy-3-(1-methylpiperidin-4-yl)-1H-indole → 3-(1-Methyl-4-piperidinyl)-1H-indol-5-ol

HRID 277992

Reaction equation

HRID 277992 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH:12]1[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]1>Br.C(O)(=O)C>[OH:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH:12]1[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]1

Participants

4

Reactant 1

HCID 113795615-methoxy-3-(1-methylpiperidin-4-yl)-1H-indole

Product 1

HCID 24383-(1-Methyl-4-piperidinyl)-1H-indol-5-olYield 85%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 260Hydrogen BromideSolvent

Procedure

A solution of 5-methoxy-3-(1-methylpiperidin-4-yl)indole (2.30 g, 9.4 mmol) in 30 mL of 30% hydrobromic acid in acetic acid was heated in a sealed tube at 105° C. for 72 hours. The reaction mixture was cooled to room temperature and concentrated in vacuo. The residue was dissolved in water, and the pH was adjusted to about 13 with 5N aqueous sodium hydroxide. The mixture was concentrated in vacuo, and the residue was chromatographed on a silica gel column, eluting with 20% 2M ammonia in methanol/dichloromethane. After concentrating in vacuo, the residue was dissolved in methanol, charged with Dowex® 50X8-200 ion-exchange resin (25 g) and stirred overnight at room temperature. The mixture was filtered, and the resin was washed with water and methanol. The Dowex® resin was stirred overnight in 100 mL of 2M ammonia in methanol and filtered. The filtrate was concentrated in vacuo to provide 1.84 g (85%) of the title compound, which was used without further purification in Preparation 17. EA calculated for C13H17N3O: C, 67.53; H, 7.36; N, 18.18. Found: C, 67.24; H, 7.37; N, 18.38.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in water
  3. concentrationThe mixture was concentrated in vacuo
  4. customthe residue was chromatographed on a silica gel column
  5. washeluting with 20% 2M ammonia in methanol/dichloromethane
  6. concentrationAfter concentrating in vacuo
  7. dissolutionthe residue was dissolved in methanol
  8. additioncharged with Dowex® 50X8-200 ion-exchange resin (25 g)
  9. filtrationThe mixture was filtered
  10. washthe resin was washed with water and methanol
  11. stirringThe Dowex® resin was stirred overnight in 100 mL of 2M ammonia in methanol
  12. filtrationfiltered
  13. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-5891096d81784696a2a8c8f73411a111
Source dataset
uspto-grants-2002_03
Patent number
US06358972B1

Linked notes

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