反应详情

温度

60 °C

Under nitrogen, to a vigorously stirred suspension of zinc dust (25.5 g, 391 mmol) in anhydrous THF (700 ml) was added chlorotrimethylsilane (10.7 ml, 85 mmol) and the suspension heated to 60° C. After 1 hour at 60° C. the reaction was allowed to cool to 40° C. and a solution of 6-fluoro-2-iodo-3,4-dimethoxybenzonitrile (as prepared in Example 1(a), 100 g, 330 mmol) was added slowly over a period of 20 minutes, keeping the temperature in the range 40° C. to 50° C. The resulting suspension was heated to 60° C. for 1 hour then allowed to cool to room temperature. 2-Bromopyridine (61.8 g, 391 mmol), palladium acetate (0.73 g, 3.3 mmol) and triphenylphosphine (1.71 g, 6.5 mmol) were added and the suspension heated to 60° C. for 1 hour then allowed to cool to room temperature. The reaction was quenched with a 5% aqueous solution of the dipotassium salt of ethylenediaminetetraacetic acid (1 liter), followed by DCM (2 liters) and the resulting mixture stirred for 15 minutes. After this time the mixture was filtered through Arbocel™ filter aid and the pad washed with DCM (100 ml). The phases were separated and the organic phase washed with water (1 liter). The organic phase was distilled and replaced with acetonitrile to give a final volume of 1 liter and the resulting solution left to cool to room temperature overnight. The resulting suspension was filtered and the solid dried in vacuo overnight at 45° C. to give 54.0 g of the title product (67%).

1. temperatureto cool to 40° C.
2. customin the range 40° C. to 50° C
3. temperatureThe resulting suspension was heated to 60° C. for 1 hour
4. temperatureto cool to room temperature
5. temperaturethe suspension heated to 60° C. for 1 hour
6. temperatureto cool to room temperature
7. customThe reaction was quenched with a 5% aqueous solution of the dipotassium salt of ethylenediaminetetraacetic acid (1 liter)
8. filtrationAfter this time the mixture was filtered through Arbocel™
9. filtrationfilter aid
10. washthe pad washed with DCM (100 ml)
11. customThe phases were separated
12. washthe organic phase washed with water (1 liter)
13. distillationThe organic phase was distilled
14. customto give a final volume of 1 liter
15. waitthe resulting solution left
16. temperatureto cool to room temperature overnight
17. filtrationThe resulting suspension was filtered
18. customthe solid dried in vacuo overnight at 45° C.