Hydrochloric Acid → 1-[4-[3-[4-[(4-Fluorophenyl)[(4-fluorophenyl)amino]methyl]-1-piperidinyl]propoxy]phenyl]-2-methyl-1-propanone dihydrochloride

HRID 1614635Notes

Reaction equation

HRID 1614635 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.[Cl:23][CH2:24][CH2:25][CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([C:34](=[O:38])[CH:35]([CH3:37])[CH3:36])=[CH:30][CH:29]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+].[ClH:47]>C(O)CCC.C(Cl)Cl>[ClH:23].[ClH:47].[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][CH2:25][CH2:26][O:27][C:28]3[CH:33]=[CH:32][C:31]([C:34](=[O:38])[CH:35]([CH3:37])[CH3:36])=[CH:30][CH:29]=3)[CH2:12][CH2:11]2)=[CH:21][CH:20]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 19771957N,alpha-bis(4-fluorophenyl)-4-piperidinemethanamineHCID 197720131-[4-(3-Chloropropoxy)phenyl]-2-methyl-1-propanone

Product 1

HCID 197720971-[4-[3-[4-[(4-Fluorophenyl)[(4-fluorophenyl)amino]methyl]-1-piperidinyl]propoxy]phenyl]-2-methyl-1-propanone dihydrochloride

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of N,α-bis(4-fluorophenyl)-4-piperidinemethanamine (4.63 g, 0.0153 mol), 1-[4-(3-chloropropoxy)phenyl]-2-methyl-1-propanone (3.69 g, 0.0153 mol), and potassium carbonate (2.76 g, 0.02 mol) was heated at reflux 16 h in 350 mL 1-butanol containing sodium iodide (0.2 g). The reaction was concentrated to dryness and partitioned between chloroform and water. The chloroform layer was then extracted with 5% sodium hydroxide and dried (Na2SO4). The chloroform was removed to give a red oil. This material was subjected to flash chromatography on silica gel using 2% methanol in methylene chloride to accomplish elution. Fractions of similar purities were combined, and solvents removed to give an oil. The oil was converted to the HCl salt and recrystallized from methanol-diethyl ether to give a white solid. This solid was dried 16 h at 78° C. in vacuo. The procedure utilized here furnished 5.26 g (59%) of white crystalline product, mp 221° -223° C. (dec.).

Workup

  1. temperaturewas heated
  2. concentrationThe reaction was concentrated to dryness
  3. custompartitioned between chloroform and water
  4. extractionThe chloroform layer was then extracted with 5% sodium hydroxide
  5. dry with materialdried (Na2SO4)
  6. customThe chloroform was removed
  7. customto give a red oil
  8. washelution
  9. customsolvents removed
  10. customto give an oil
  11. customrecrystallized from methanol-diethyl ether
  12. customto give a white solid
  13. customThis solid was dried 16 h at 78° C. in vacuo

Sources & evidence

ORD record
ord-7f2b906195254c3ca0add4bbea859e38
Source dataset
uspto-grants-1993_03
Patent number
US05198449

Reaction notes

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