1-Benzyl-4-((4-chlorophenyl)amino)piperidine-4-carbonitrile → HCID 23136852, compound

HRID 556957Notes

Reaction equation

HRID 556957 reaction equation
C([N:8]1[CH2:13][CH2:12][C:11]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)([C:14]#[N:15])[CH2:10][CH2:9]1)C1C=CC=CC=1.ClC(OC(Cl)C)=O.ClC([O-])=O>ClC(Cl)C>[Cl:23][C:20]1[CH:19]=[CH:18][C:17]([NH:16][C:11]2([C:14]#[N:15])[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]2)=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 704181-Benzyl-4-((4-chlorophenyl)amino)piperidine-4-carbonitrileHCID 5213051-Chloroethyl chloroformateHCID 21226386Carbonochloridate

Product 1

HCID 23136852HCID 23136852, compoundYield 71.2%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To 1-Benzyl-4-(4-chloro-phenylamino)-piperidine-4-carbonitrile (163 mg, 0.5002 mmol) in dichloroethane (5 ml) was added 1-chloroethyl chloroformate (65 μl, 0.600 mmol). The mixture was heated to reflux and stirred under N2. After 1 hour 15 minutes, an additional 86 μl (0.800 mmol) of the chloroformate was added to the reaction and stirred for an additional 2 hours at reflux. After cooling to room temperature the reaction was concentrated under reduced pressure. To this residue was added methanol (5 ml) and the reaction was heated at reflux for 2 hours. Next, the reaction was allowed to cool to room temperature and concentrated under reduced pressure. The residue was diluted with ethyl acetate and water. The organic layer was removed and sodium hydroxide (1N) was added to the aqueous layer until pH≈9. The aqueous layer was extracted with ethyl acetate 2 times and dried over magnesium sulfate. The solvent was distilled off under reduced pressure to obtain the title compound (84 mg, 71%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux
  3. stirringstirred for an additional 2 hours
  4. temperatureat reflux
  5. concentrationwas concentrated under reduced pressure
  6. additionTo this residue was added methanol (5 ml)
  7. temperaturethe reaction was heated
  8. temperatureat reflux for 2 hours
  9. temperatureto cool to room temperature
  10. concentrationconcentrated under reduced pressure
  11. additionThe residue was diluted with ethyl acetate and water
  12. customThe organic layer was removed
  13. additionsodium hydroxide (1N) was added to the aqueous layer until pH≈9
  14. extractionThe aqueous layer was extracted with ethyl acetate 2 times
  15. dry with materialdried over magnesium sulfate
  16. distillationThe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-4b0884ff2c7a4ec2b76dfd76adac96cb
Source dataset
uspto-grants-2011_11
Patent number
US08058287B2

Reaction notes

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