反应详情

温度

80 °C

A mixture of tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (1.0 g, 3.02 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (0.206 g, 0.302 mmol), and copper(I) iodide (0.115 g, 0.603 mmol) in a dry microwave vial was flushed with nitrogen. N,N-dimethylacetamide (3 mL) was added followed by (1-(tert-butoxycarbonyl)piperidin-4-yl)zinc(II) iodide (9.52 mL, 9.05 mmol, approximately 1 M solution in N,N-dimethylacetamide prepared as described in the Journal of Organic Chemistry, 2004, 69, 5120). The vial was sealed and heated at 80° C. overnight. After cooling to RT, the reaction was partitioned between EtOAc and sat. aq. NH4Cl solution. This was left stirring for 30 min. The aqueous phase was washed with EtOAc and the combined organic phases were washed with brine and dried with sodium sulfate. Removal of the solvents followed by radial silica gel chromatography eluting with hexane containing 5 to 30% EtOAc afforded tert-butyl 4-(3-((tert-butoxycarbonyl)amino)-2-chloro-5-cyanophenyl)piperidine-1-carboxylate (0.376 g) as a white solid.

1. customwas flushed with nitrogen
2. additionN,N-dimethylacetamide (3 mL) was added
3. customprepared
4. customThe vial was sealed
5. temperatureAfter cooling to RT
6. customthe reaction was partitioned between EtOAc and sat. aq. NH4Cl solution
7. waitThis was left
8. washThe aqueous phase was washed with EtOAc
9. washthe combined organic phases were washed with brine
10. dry with materialdried with sodium sulfate
11. customRemoval of the solvents
12. washeluting with hexane containing 5 to 30% EtOAc