反应详情

温度

-20 °C

A flask equipped with an overhead stirrer, thermometer and addition funnel was placed under a nitrogen atmosphere then charged with tert-butyl hydrogen peroxide (TBHP; 95 mL, 5.5 M, 522 mmol) and tetrahydrofuran (THF; 200 mL). The reaction was cooled to −20±5° C. and n-butyl lithium (n-BuLi; 235 mL, 2.5 M, 587 mmol) was charged to the addition funnel and slowly added, keeping the reaction temperature below −5±5° C. Upon completion of addition the reaction was warmed to 0±5° C. and the amide of Example 4 (19.80 g, 130 mmol) in THF (20 mL) was added maintaining the temperature at 0±5° C. after which the temperature was increased to 25±5° C. and the reaction stirred for 12 hours. After this time IPAc (200 mL) and saturated aqueous sodium hydrosulfite (200 mL) were added and the reaction stirred for 60 min. The layers were separated and the aqueous layer extracted with IPAc (twice, 75 mL each). The combined organic phases were dried over sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure to provide the title compound (21.87 g, 99%).

1. customA flask equipped with an overhead stirrer
2. additionthermometer and addition funnel
3. additionslowly added
4. customthe reaction temperature below −5±5° C
5. additionUpon completion of addition the reaction
6. temperaturewas warmed to 0±5° C.
7. temperaturemaintaining the temperature at 0±5° C. after which the temperature
8. temperaturewas increased to 25±5° C.
9. stirringthe reaction stirred for 60 min
10. customThe layers were separated
11. extractionthe aqueous layer extracted with IPAc (twice, 75 mL each)
12. dry with materialThe combined organic phases were dried over sodium sulfate (Na2SO4)
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure