反应详情

温度

-72 °C

1,3,5-Tribromo-benzene (31.4 g, 100 mmol) was dissolved under argon in a flame dried three-neck flask in 1000 mL diethylether and the solution was cooled to −72° C. A solution of 62 mL nBuLi (1.6 M in hexane, 100 mmol) was added to the resulting suspension in such a fashion that temperature did not rise above −70° C. The mixture was stirred for 30 min at −75° C. and the reaction was monitored by HPLC. A solution of 10.4 g (100 mmol) 3-cyanopyridine in 100 mL diethylether was added in such a fashion that temperature did not rise above −71° C. The mixture was stirred at −75° C. for 60 min and the reaction was monitored by HPLC. The cooling bath was removed and warmed to −25° C. 2 N HCl (250 mL) was added and the mixture was stirred for 20 min at room temperature. The mixture was made alkaline by addition of 1 N NaOH. The product was extracted with ethyl acetate and the combined organic layers were dried over Na2SO4. The product was purified by chromatography (700 g silica agel, CH2Cl2, then CH2Cl2/ethyl acetate 1:1, UV) to yield 27.7 g (81%) of (3,5-dibromo-phenyl)-pyridin-3-yl-methanone.

1. dry with materialdried three-neck flask in 1000 mL diethylether
2. customdid not rise above −70° C
3. customdid not rise above −71° C
4. stirringThe mixture was stirred at −75° C. for 60 min
5. customThe cooling bath was removed
6. temperaturewarmed to −25° C
7. addition2 N HCl (250 mL) was added
8. stirringthe mixture was stirred for 20 min at room temperature
9. additionby addition of 1 N NaOH
10. extractionThe product was extracted with ethyl acetate
11. dry with materialthe combined organic layers were dried over Na2SO4
12. customThe product was purified by chromatography (700 g silica agel, CH2Cl2