Hydrochloric Acid → N-(3,4-Difluorophenyl)-alpha-(4-fluorophenyl)-1-[2-(2-naphthalenyloxy)ethyl]-4-piperidinemethanamine dihydrochloride

HRID 1614641Notes

Reaction equation

HRID 1614641 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:9][CH:10]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[CH:5]=[CH:6][C:7]=1[F:8].Br[CH2:25][CH2:26][O:27][C:28]1[CH:37]=[CH:36][C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH:29]=1.C(=O)(O)[O-].[Na+].[I-].[Na+].[ClH:45]>C(O)CCC>[ClH:45].[ClH:45].[F:1][C:2]1[CH:3]=[C:4]([NH:9][CH:10]([C:17]2[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=2)[CH:11]2[CH2:16][CH2:15][N:14]([CH2:25][CH2:26][O:27][C:28]3[CH:37]=[CH:36][C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH:29]=3)[CH2:13][CH2:12]2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 516892Sodium BicarbonateHCID 6406922-(2-Bromoethoxy)naphthaleneHCID 197720314-[[(3,4-Difluorophenyl)amino](4-fluorophenyl)methyl]piperidine

Product 1

HCID 19771926N-(3,4-Difluorophenyl)-alpha-(4-fluorophenyl)-1-[2-(2-naphthalenyloxy)ethyl]-4-piperidinemethanamine dihydrochloride

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A mixture of 4.20 g (0.010 mol) of 4-[[(3,4-difluorophenyl)amino](4-fluorophenyl)methyl]piperidine, 2.90 g (0.012 mol) of 2-(2-bromoethoxy)naphthalene, 8.1 g (0.096 mol) of sodium bicarbonate, and a trace of sodium iodide in 400 mL of 1-butanol was heated at reflux for 16 h. The solvent was removed in vacuo, and the residue was partitioned between CH2Cl2 and dilute NaOH. The CH2Cl2 solution was dried (Na2SO4), and the solvent was removed in vacuo to give a gum. This was subjected to flash column chromatography (silica gel, eluted with CH2Cl2 and 1-2% MeOH in CH2Cl2) to give the free base. This was converted to the HCl salt, and the salt was recrystallized from diethyl ether/MeOH to give 3.05 g (54.1%) as a white crystalline solid: mp 210°-215° C.

Workup

  1. temperatureat reflux for 16 h
  2. customThe solvent was removed in vacuo
  3. customthe residue was partitioned between CH2Cl2 and dilute NaOH
  4. dry with materialThe CH2Cl2 solution was dried (Na2SO4)
  5. customthe solvent was removed in vacuo
  6. customto give a gum
  7. washThis was subjected to flash column chromatography (silica gel, eluted with CH2Cl2 and 1-2% MeOH in CH2Cl2)
  8. customto give the free base
  9. customthe salt was recrystallized from diethyl ether/MeOH
  10. customto give 3.05 g (54.1%) as a white crystalline solid

Sources & evidence

ORD record
ord-ca8749dc7000432abbb84394a57be8e6
Source dataset
uspto-grants-1993_03
Patent number
US05198449

Reaction notes

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