Cesium carbonate → 1,1-Dimethylethyl 4-[(3-cyanophenyl)amino]-1-piperidinecarboxylate

Temperature

105 °C

A mixture of BINAP (560 mg, 0.9 mmol), palladium acetate (135 mg, 0.6 mmol) and cesium carbonate (2.932 g, 9 mmol) in 1,4-dioxane (10 ml) was sonicated for 50 minutes. 1,1-Dimethylethyl 4-amino-1-piperidinecarboxylate (1.2 g, 6 mmol) and 3-bromobenzonitrile (1.638 g, 9 mmol) were added and the mixture heated to 105° C. overnight under an argon atmosphere. On cooling, the solvent was removed in vacuo and the residue partitioned between water (100 ml) and EtOAc (100 ml). The organic layer was separated, dried and concentrated and the crude product purified by chromatography. Elution with a 0-50% Et2O/petroleum ether gradient gave the title compound as a white solid (1.49 g). δH (CDCl3, 250 MHz) 7.22 (2H, t), 6.95 (1H, dd), 6.77 (2H, m), 4.07 (2H, m), 3.77 (1H, m), 3.41 (1H, m), 3.20 (1H, m), 2.93 (2H, m), 2.03 (2H, m), 1.47 (9H, s), 1.34 (2H, m). MS (ES): MH+ 302.

1. customwas sonicated for 50 minutes
2. temperatureOn cooling
3. customthe solvent was removed in vacuo
4. customthe residue partitioned between water (100 ml) and EtOAc (100 ml)
5. customThe organic layer was separated
6. customdried
7. concentrationconcentrated
8. customthe crude product purified by chromatography
9. washElution with a 0-50% Et2O/petroleum ether gradient

ORD record

ord-9a54a3b366f844a18f94b9db04f87ad0

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08536182B2