4-Fluoroaniline → 1-Benzyl-4-((4-fluorophenyl)amino)piperidine-4-carbonitrile

HRID 458139Notes

Reaction equation

HRID 458139 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=1.C[Si]([C:27]#[N:28])(C)C.[OH-].[Na+]>C(O)(=O)C>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([NH:20][C:19]2[CH:21]=[CH:22][C:16]([F:15])=[CH:17][CH:18]=2)([C:27]#[N:28])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 97314-FluoroanilineHCID 14798Sodium HydroxideHCID 192201-Benzyl-4-piperidoneHCID 82115Trimethylsilyl cyanide

Product 1

HCID 30172221-Benzyl-4-((4-fluorophenyl)amino)piperidine-4-carbonitrile

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 120 g (634 mmol) 1-benzyl-4-piperidone, 77.5 g (697 mmol) 4-fluoroaniline and 62.9 g (634 mmol) trimethylsilyl cyanide in 400 ml acetic acid was stirred at ambient temperature for 18 h. The reaction mixture was poured onto 500 g ice, pH is adjusted to 9 by addition of 5N NaOH and the aqueous mixture extracted with dichloromethane. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and evaporated. The crystalline residue was re-crystallised from Et2O: 152 g 1-benzyl-4-(4-fluoro-phenylamino)-piperidine-4-carbonitrile as colorless crystals: MS (ISP): 310.1 MH+.

Workup

  1. extractionthe aqueous mixture extracted with dichloromethane
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe crystalline residue was re-crystallised from Et2O

Sources & evidence

ORD record
ord-49d43f6400e2406b95dd31038f5cab2f
Source dataset
uspto-grants-2007_03
Patent number
US07189850B2

Reaction notes

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