Hydrochloric Acid → 4-[(4-Fluorophenyl)[(4-fluorophenyl)amino]methyl]-alpha-(phenoxymethyl)-1-piperidineethanol dihydrochloride hemihydrate

HRID 1614626Notes

Reaction equation

HRID 1614626 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1.[O:23]1[CH:25]([CH2:26][O:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:24]1.[ClH:34]>C(#N)C>[OH2:23].[ClH:34].[ClH:34].[F:22][C:19]1[CH:18]=[CH:17][C:16]([CH:9]([NH:8][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH:10]2[CH2:15][CH2:14][N:13]([CH2:24][CH:25]([CH2:26][O:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[OH:23])[CH2:12][CH2:11]2)=[CH:21][CH:20]=1.[F:22][C:19]1[CH:18]=[CH:17][C:16]([CH:9]([CH:10]2[CH2:15][CH2:14][N:13]([CH2:24][CH:25]([CH2:26][O:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[OH:23])[CH2:12][CH2:11]2)[NH:8][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)=[CH:21][CH:20]=1.[ClH:34].[ClH:34]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 31217Phenyl glycidyl etherHCID 19771957N,alpha-bis(4-fluorophenyl)-4-piperidinemethanamine

Product 1

HCID 1317178404-[(4-Fluorophenyl)[(4-fluorophenyl)amino]methyl]-alpha-(phenoxymethyl)-1-piperidineethanol dihydrochloride hemihydrateYield 53%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 3.41 g (11.3 mmol) of the N,α-bis(4-fluorophenyl)-4-piperidinemethanamine and 2.20 g (14.7 mmol) of 1,2-epoxy-3-phenoxypropane in 400 mL of acetonitrile was heated at reflux for 46 h. The solvent was removed in vacuo, and the residue was subjected to flash chromatography (silica gel, eluted with 3% CH3OH in CH2Cl2) to give an oil. This was converted to the HCl salt, and the salt was recrystallized from CH3OH-ether to give give 3.20 g (53%) of a crystalline white solid, mp 229°-232° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 46 h
  3. customThe solvent was removed in vacuo
  4. washthe residue was subjected to flash chromatography (silica gel, eluted with 3% CH3OH in CH2Cl2)
  5. customto give an oil
  6. customthe salt was recrystallized from CH3OH-ether
  7. customto give

Sources & evidence

ORD record
ord-eec900594e8548db9e56dd7b014ff32e
Source dataset
uspto-grants-1993_03
Patent number
US05198449

Reaction notes

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