Potassium Carbonate → 1-(4-Indolyloxy)-3-[4-hydroxy-4-(6-hydroxynaphth-2-yl)piperidine-1-yl]propane

HRID 1416200Notes

Reaction equation

HRID 1416200 reaction equation
[NH:1]1[C:9]2[C:4](=[C:5]([O:10][CH2:11][CH2:12][CH2:13]Cl)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[OH:15][C:16]1([C:22]2[CH:31]=[CH:30][C:29]3[C:24](=[CH:25][CH:26]=[C:27]([OH:32])[CH:28]=3)[CH:23]=2)[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[NH:1]1[C:9]2[C:4](=[C:5]([O:10][CH2:11][CH2:12][CH2:13][N:19]3[CH2:20][CH2:21][C:16]([OH:15])([C:22]4[CH:31]=[CH:30][C:29]5[C:24](=[CH:25][CH:26]=[C:27]([OH:32])[CH:28]=5)[CH:23]=4)[CH2:17][CH2:18]3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 116941694-(3-chloropropoxy)-1H-indoleHCID 538687414-Hydroxy-4-(6-hydroxynaphth-2-yl)piperidine

Product 1

HCID 675737501-(4-Indolyloxy)-3-[4-hydroxy-4-(6-hydroxynaphth-2-yl)piperidine-1-yl]propaneYield 25%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 0.172 gm (0.82 mMol) 1-(4-indolyloxy)-3-chloropropane, 0.200 gm (0.82 mMol) 4-hydroxy-4-(6-hydroxynaphth-2-yl)piperidine, and 0.17 gm (1.2 mMol) potassium carbonate in 6 mL acetonitrile were stirred at reflux for 18 hours. The reaction mixture was cooled to room temperature and then partitioned between ethyl acetate and 2N sodium hydroxide. The phases were separated and the aqueous phase extracted well with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was subjected to radial chromatography (silica, 2 mm plate), eluting with 2% methanol in dichloromethane containing a trace of ammonium hydroxide. Fractions shown to contain product were combined and concentrated under reduced pressure to provide 0.085 gm (25%) 1-(4-indolyloxy)-3-[4-hydroxy-4-(6-hydroxynaphth-2-yl)piperidine-1-yl]propane as a foam. The oxalate salt was prepared to provide the title compound.

Workup

  1. temperatureat reflux for 18 hours
  2. custompartitioned between ethyl acetate and 2N sodium hydroxide
  3. customThe phases were separated
  4. extractionthe aqueous phase extracted well with ethyl acetate
  5. washThe combined organic phases were washed with saturated aqueous sodium chloride
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. washeluting with 2% methanol in dichloromethane containing a trace of ammonium hydroxide
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2806cfc3ddd6451a887f7816a962b43f
Source dataset
uspto-grants-1999_06
Patent number
US05912256

Reaction notes

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