反应详情

温度

-20 °C

To a solution of 101c (50 g, 0.22 mol) in anhydrous THF (750 mL) was added 2.4 M solution of n-butyllithium in hexane (225 mL) at −78° C. under nitrogen atmosphere. The clear amber solution was warmed to −20° C. and stirred for 4 hr. The reaction mixture became red-amber and cloudy. The mixture was re-cooled to −78° C. and stirred rapidly before 72 mL of DMF was added drop wise at such a rate that the temperature was controlled below −60° C. After the addition, the reaction mixture was stirred at −78° C. for 15 min then stirred at −20° C. for 1 hr and room temperature for 1 hr. The reaction mixture was quenched with 200 mL of 0.5 M aqueous KHSO4. More KHSO4 solution was added in until the pH was adjusted to 4-5. The aqueous phase was extracted with EtOAc (3×500 mL) and the combined organic phases was washed with 400 mL of brine and dried over Na2SO4, filtered and concentrated in vacuo to give 101d (35 g, 62%) as a yellow solid which was used in the next step without further purification. LCMS, ESI, m/z 260 (M+1)+.

1. temperatureThe mixture was re-cooled to −78° C.
2. additionwas added drop wise at such a rate that the temperature
3. customwas controlled below −60° C
4. additionAfter the addition
5. stirringthe reaction mixture was stirred at −78° C. for 15 min
6. stirringthen stirred at −20° C. for 1 hr and room temperature for 1 hr
7. customThe reaction mixture was quenched with 200 mL of 0.5 M aqueous KHSO4
8. additionMore KHSO4 solution was added in until the pH
9. extractionThe aqueous phase was extracted with EtOAc (3×500 mL)
10. washthe combined organic phases was washed with 400 mL of brine
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated in vacuo