Bromobenzene → 1,4-Diphenylpiperidine-4-carbonitrile

HRID 645489Notes

Reaction equation

HRID 645489 reaction equation
Cl.[C:2]1([C:8]2([C:14]#[N:15])[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C1(C)C=CC=CC=1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:17]1([N:11]2[CH2:10][CH2:9][C:8]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)([C:14]#[N:15])[CH2:13][CH2:12]2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

8

Reactant 4

HCID 7961BromobenzeneHCID 80271Tri-o-tolylphosphineHCID 30849734-Phenylpiperidine-4-carbonitrile hydrochlorideHCID 23676156Sodium t-butoxide

Product 1

HCID 130468601,4-Diphenylpiperidine-4-carbonitrile

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a suspension of 4-phenylpiperidine-4-carbonitrile hydrochloride (6.7 mmol) in toluene (30 mL) are successively added bromobenzene (8.0 mmol), sodium tert-butoxide (17 mmol), tri-o-tolylphosphine (1.3 mmol), and tris(dibenzylideneacetone)dipalladium (0.7 mmol), then the mixture is refluxed for 20 h. The reaction mixture is cooled, diluted with water, then extracted with AcOEt. The organic extracts are washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue is purified by silica gel column chromatography to give the title compound; 1H NMR (CDCl3) δ: 2.12-2.20 (2H, m), 2.23-2.28 (2H, m), 2.94-3.01 (2H, m), 3.86 (2H, d), 6.83 (1H, t), 7.04 (2H, d), 7.22-7.28 (2H, m), 7.36-7.41 (1H, m), 7.45-7.49 (2H, m), 7.56-7.59 (2H, m).

Workup

  1. temperaturethe mixture is refluxed for 20 h
  2. temperatureThe reaction mixture is cooled
  3. extractionextracted with AcOEt
  4. washThe organic extracts are washed with water and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified by silica gel column chromatography

Sources & evidence

ORD record
ord-45b9102dabb749708028189b5dcedefc
Source dataset
uspto-grants-2010_04
Patent number
US07704996B2

Reaction notes

Loading…