Bromobenzene → 1,4-Diphenylpiperidine-4-carbonitrile

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).

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

ORD record

ord-45b9102dabb749708028189b5dcedefc

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07704996B2