反应详情

温度

-78 °C

To a solution containing 25 g (140 mmol) of the product from Step A and 52.2 mL (350 mmol) of redistilled N,N,N′,N′-tetramethylethylenediamine in 350 mL of dry THF under nitrogen at −78° C. was slowly added via cannula 140 mL (350 mmol) of n-butyllithium (2.5N in hexane). The reaction mixture was stirred at −78° C. for 30 min then at −10° C. for 90 min. The reaction mixture was then cooled to −78° C. and 30.2 mL (350 mmol) of 1,2-dibromoethane was slowly added. The mixture was stirred at −78° C. for 30 min, at −10° C. for 90 min then quenched with saturated aqueous ammonium chloride solution. A 600 mL portion of ethyl acetate was next added and the mixture was washed sequentially with water and saturated aqueous brine (400 mL each). The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo. The crude material was purified by flash chromatography on a Biotage Horizon® system (silica gel, 0 to 100% ethyl acetate/hexanes gradient) to give the title compound. 1H NMR (500 MHz, CDCl3): δ 9.54 (s, 1H), 8.18 (d, J=5.2 Hz, 1H), 7.86 (br s, 1H), 7.51 (d, J=5.3 Hz, 1H), 1.39 (s, 9H).

1. waitat −10° C. for 90 min
2. temperatureThe reaction mixture was then cooled to −78° C.
3. stirringThe mixture was stirred at −78° C. for 30 min, at −10° C. for 90 min
4. customthen quenched with saturated aqueous ammonium chloride solution
5. additionA 600 mL portion of ethyl acetate was next added
6. washthe mixture was washed sequentially with water and saturated aqueous brine (400 mL each)
7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
8. filtrationfiltered
9. customevaporated in vacuo
10. customThe crude material was purified by flash chromatography on a Biotage Horizon® system (silica gel, 0 to 100% ethyl acetate/hexanes gradient)