反应详情

温度

30 °C

To a solution of 4-(trifluoromethyl)phenylboronic acid (116.52 g, 613.5 mmol) in 1,2-dimethoxyethane (1200 mL) was added 2,4-dichloro-6-methylpyrimidine (100 g, 613.5 mmol). To this stirring solution was added a solution of sodium carbonate (195.07 g, 1840.5 mmol) dissolved in water (600 mL) giving some precipitation of the base and then bis(triphenylphosphine)palladium (II) dichloride (2.15 g, 3.07 mmol). The mixture was brought to 50° C. over about 1 hr then stirred at this temperature overnight. The reaction mixture cooled to approx. 30° C., filtered and washed with DCM (approx. 500 mL). The filtrate was evaporated to remove the bulk of the organic solvents. To the residues was added DCM (250 mL) and the phases were separated. The aqueous phase was extracted with DCM (2×250 mL) and the combined extracts were washed with brine (250 mL), dried over magnesium sulphate, filtered and evaporated to a brown gummy solid. The solid was stirred in iso-hexane (150 mL) at 60° C. until the solid had dissolved. The heat was turned off and the flask allowed to cool in the heat-on block naturally. When the solution was at 30° C. seed crystals were added causing immediate crystallisation. The mixture was stood overnight then the crystalline material was crushed and filtered. The solids were washed with cold iso-hexane (2×50 mL) and dried to give the title compound (D11) as a slightly sticky tan solid, (96.17 g) consistent by NMR with that prepared by Method 1.

1. customgiving
2. customsome precipitation of the base
3. filtrationfiltered
4. washwashed with DCM (approx. 500 mL)
5. customThe filtrate was evaporated
6. customto remove the bulk of the organic solvents
7. additionTo the residues was added DCM (250 mL)
8. customthe phases were separated
9. extractionThe aqueous phase was extracted with DCM (2×250 mL)
10. washthe combined extracts were washed with brine (250 mL)
11. dry with materialdried over magnesium sulphate
12. filtrationfiltered
13. customevaporated to a brown gummy solid
14. stirringThe solid was stirred in iso-hexane (150 mL) at 60° C. until the solid
15. dissolutionhad dissolved
16. temperatureto cool in the heat-on block naturally
17. customwas at 30° C.
18. additionwere added
19. customcrystallisation
20. waitThe mixture was stood overnight
21. customthe crystalline material was crushed
22. filtrationfiltered
23. washThe solids were washed with cold iso-hexane (2×50 mL)
24. customdried