反应详情

温度

32.5 °C

To a suspension of epothilone F (5.0 g, 9.55 mmol, 86.2% potency) and diphenylphosphoryl azide (2.27 ml, 10.5 mmol, 1.1 eq) in tetrahydrofuran (40 ml) was added gradually 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 1.71 ml, 11.46 mmol, 1.2 eq) and the reaction subsequently stirred at 25-40° C. for 4-6 hrs. To the reaction mixture was then added a 6.0 M solution of ammonium acetate (7.96 ml, 47.7 mmol, 5 eq) followed by 1.0 M trimethylphosphine/tetrahydrofuran solution (1.5 eq). The reaction mixture was diluted with water and the aqueous phase extracted with three portions of ethyl acetate (40 ml each). The organic phase was then washed with three portions of diluted ammonium hydroxide (40 ml each). The combined aqueous washes are then extracted with two portions of ethyl acetate (40 ml each). The combined ethyl acetate phases are washed with two portions of water (20 ml each) then concentrated and azeotropically dried under reduced pressure to a final volume of 60 ml. The resulting solution was heated at 65-75° C. and 70 ml n-heptane was added slowly. The mixture was allowed to cool slowly and stirred at a final temperature of 15-20° C. The resulting solid (3.34 g, 78% corrected for input potency) was isolated by filtration followed by vacuum drying to afford crystalline product.

1. customthe reaction
2. extractionthe aqueous phase extracted with three portions of ethyl acetate (40 ml each)
3. washThe organic phase was then washed with three portions of diluted ammonium hydroxide (40 ml each)
4. extractionThe combined aqueous washes are then extracted with two portions of ethyl acetate (40 ml each)
5. washThe combined ethyl acetate phases are washed with two portions of water (20 ml each)
6. concentrationthen concentrated
7. customazeotropically dried under reduced pressure to a final volume of 60 ml
8. temperatureThe resulting solution was heated at 65-75° C.
9. addition70 ml n-heptane was added slowly
10. temperatureto cool slowly
11. stirringstirred at a final temperature of 15-20° C
12. customThe resulting solid (3.34 g, 78% corrected for input potency) was isolated by filtration
13. customdrying
14. customto afford crystalline product