反应详情

温度

90 °C

5-Bromo-N-((1S,2R)-2-hydroxy-cyclohexyl)-6-(2,2,2-trifluoro-ethoxy)-nicotinamide (42.0 g, 106 mmol) was dissolved in toluene (1900 mL) and DMF (100 mL). To this solution was added with stirring [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) CH2Cl2 (0.9 g, 1.06 mmol), 3,4-dichlorophenylboronic acid (20.2 g, 106 mmol) and sodium carbonate solution (2M, 106 mL). This mixture was heated to 90° C. for 2 h, cooled to room temperature and partitioned between ethyl acetate (1000 mL) and water (2000 mL), the water phase was separated, extracted twice more with ethyl acetate (2×1000 mL) and the organic phases were washed once with water and once with brine (1000 mL each). Organic phases were pooled, dried with MgSO4 and the volatiles removed in vacuo. The residue was dissolved in diethyl ether (500 mL) and filtered through diatomaceous earth. The title compound precipitated when n-heptane (500 mL) was added drop wise to the diethyl ether solution, was filtered off and dried in vacuo to give 33.3 g the title compound as an off-white solid; MS 463.079 (M+H)+.

1. temperaturecooled to room temperature
2. custompartitioned between ethyl acetate (1000 mL) and water (2000 mL)
3. customthe water phase was separated
4. extractionextracted twice more with ethyl acetate (2×1000 mL)
5. washthe organic phases were washed once with water and once with brine (1000 mL each)
6. dry with materialdried with MgSO4
7. customthe volatiles removed in vacuo
8. dissolutionThe residue was dissolved in diethyl ether (500 mL)
9. filtrationfiltered through diatomaceous earth
10. customThe title compound precipitated when n-heptane (500 mL)
11. additionwas added drop wise to the diethyl ether solution
12. filtrationwas filtered off
13. customdried in vacuo