反应详情

温度

80 °C

To a solution of methyl 2-{[(4-fluorophenyl)methyl]oxy}-5-iodobenzoate (may be prepared as described in Description 112; 1.4 g, 3.63 mmol) in 1,2-dimethoxyethane (40 ml) was added 1,1-dimethylethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (3.20 g, 10.88 mmol), tripotassium phosphate (1.54 g, 7.25 mmol), PdCl2(dppf) (0.16 g, 0.22 mmol) and the mixture was heated to 80° C. for 6 hours. The temperature was raised to 90° C. for 2 hours. Further catalyst was added and the mixture was divided into two. One 20 ml portion was subjected to 120° C. for 30 min under microwave conditions. The second portion of 20 ml was heated to reflux for 12 hrs. The 1,1-dimethylethyl carboxylate protected products were deprotected. The products were then combined and evaporated under reduced pressure on a buchi. The mixture was taken up into dichloromethane (20 ml), treated with trifluoroacetic acid (10 ml) and stirred at room temperature for 1 hour. The mixture was evaporated and purified using the Flashmaster eluting with 0-25% methanol/dichloromethane to yield the title compound. 1.15 g.

1. temperatureThe temperature was raised to 90° C. for 2 hours
2. additionFurther catalyst was added
3. temperatureThe second portion of 20 ml was heated
4. temperatureto reflux for 12 hrs
5. customevaporated under reduced pressure on a buchi
6. additiontreated with trifluoroacetic acid (10 ml)
7. customThe mixture was evaporated
8. custompurified
9. washeluting with 0-25% methanol/dichloromethane