反应详情

温度

65 °C

Water (253 mL) and THF (842 mL) were put in the reaction balloon. The reagents were added one by one to the stirred reaction mixture: potassium phosphate monohydrate 86.2 g (374 mmol) and BTEAC 2.25 g (9.88 mmol). Then 3-chloro-6-iodopyridazine, 45 g (187.2 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole, 46.73 g (224.6 mmol) were added and finally triphenylphosphine, 1.96 g (7.49 mmol) and palladiumdiacetate, 420 mg (1.87 mmol) were added. The reaction mixture was heated at 65° C. for 16 h. The reaction mixture was allowed to cool to 60° C. Then 935 mL water and 301.5 g sodium chloride were added. The mixture was stirred for 15 minutes and allowed to cool to 45° C. The phases were separated and the organic layer was washed with a solution of 45 g sodium chloride in 374 mL water. The organic layer was separated and stirred with magnesium sulphate (225 g) and charcoal (4.5 g). The mixture was filtered and evaporated. The evaporation residue was co-evaporated with toluene twice and evaporated further till a final volume of 200 ml. This residue was stirred for 16 h at room temperature. The resulting solids were collected by filtration. The solids were dried at reduced pressure affording 29.7 g of the title compound (152.6 mmol, yield 82%).

1. additionThe reagents were added one by one
2. customto the stirred reaction mixture
3. temperatureto cool to 60° C
4. temperatureto cool to 45° C
5. customThe phases were separated
6. washthe organic layer was washed with a solution of 45 g sodium chloride in 374 mL water
7. customThe organic layer was separated
8. stirringstirred with magnesium sulphate (225 g) and charcoal (4.5 g)
9. filtrationThe mixture was filtered
10. customevaporated
11. customevaporated further till a final volume of 200 ml
12. stirringThis residue was stirred for 16 h at room temperature
13. filtrationThe resulting solids were collected by filtration
14. customThe solids were dried at reduced pressure