4-Chloroaniline → 1-Benzyl-4-((4-chlorophenyl)amino)piperidine-4-carbonitrile

HRID 1983671Notes

Reaction equation

HRID 1983671 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.[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=1.C[Si]([C:27]#[N:28])(C)C.[OH-].[NH4+]>C(O)(=O)C.O>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([NH:22][C:19]2[CH:20]=[CH:21][C:16]([Cl: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

7

Reactant 4

HCID 78124-ChloroanilineHCID 14923Ammonium HydroxideHCID 192201-Benzyl-4-piperidoneHCID 82115Trimethylsilyl cyanide

Product 1

HCID 704181-Benzyl-4-((4-chlorophenyl)amino)piperidine-4-carbonitrileYield 81%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

To a solution of 1-Benzyl-piperidin-4-one (2.68 g, 14.20 mmol) in acetic acid (13 ml, glacial) was added 4-Chloro-phenylamine (1.99 g, 15.6 mmol). The reaction was cooled in a cool temperature water bath. Trimethylsilylcyanide (1.89 ml, 14.20 mmol) was added slowly. The reaction mixture was allowed to warm to room temperature and stir overnight under N2. The reaction was cooled to 0° C. Concentrated ammonium hydroxide (15 ml) was added slowly. Next added was cold water. The pH of the mixture was ≈10. The mixture was extracted three times with methylene chloride, and the organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Ether was added to the residue, and the white solid was filtered off and dried under high vacuum to give the titled compound (3.73 g, 81%)

Workup

  1. temperatureThe reaction was cooled in a cool temperature water bath
  2. temperatureThe reaction was cooled to 0° C
  3. additionNext added
  4. extractionThe mixture was extracted three times with methylene chloride
  5. dry with materialthe organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. additionEther was added to the residue
  9. filtrationthe white solid was filtered off
  10. customdried under high vacuum

Sources & evidence

ORD record
ord-22a29f77e90a402cbc8ba6f464f99f24
Source dataset
uspto-grants-2009_06
Patent number
US07541365B2

Reaction notes

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