反应详情

Trifluoromethanesulphonic anhydride (45.4 mL) is dropped into a solution of prasterone acetate (100 g) and 2,6-di-tert-butyl-4-methylpyridine (58 g) in methylene chloride (1 L) at −5° C., maintaining the temperature between −5° C. and 0° C. and stirring at said temperature for about 5 h. The mixture is then concentrated under vacuum, and the concentrate is taken up in n-hexane (about 1500 mL) to obtain a precipitate which is isolated by filtration. The filtered solution is washed with a 1N hydrochloric acid solution (about 1.5 L) and then with a sodium chloride saturated aqueous solution (500 mL). The organic phase is added with potassium carbonate (50 g), and the resulting suspension is stirred for about 15 h at room temperature, then filtered. After removal of the solvent under vacuum an oil (about 110 g) is obtained, which is taken up with tetrahydrofuran (1.5 L). The solution is degassed and diethyl(3-pyridyl)borane (54.5 g), bis(triphenylphosphine)palladium II chloride (1.8 g) and a 2M sodium carbonate aqueous solution (500 mL) are added in sequence in an inert gas environment. The resulting mixture is refluxed for about 1 h, then cooled to room temperature, and ethyl acetate (1 L) and water (1 L) are added. The aqueous phase is back-extracted with ethyl acetate (0.5 L), and the combined organic phases are concentrated under vacuum to obtain crude abiraterone acetate as oil (230 g; purity about 88%; assay 35%).

1. temperaturemaintaining the temperature between −5° C. and 0° C.
2. customfor about 5 h
3. concentrationThe mixture is then concentrated under vacuum
4. customto obtain a precipitate which
5. customis isolated by filtration
6. washThe filtered solution is washed with a 1N hydrochloric acid solution (about 1.5 L)
7. additionThe organic phase is added with potassium carbonate (50 g)
8. stirringthe resulting suspension is stirred for about 15 h at room temperature
9. filtrationfiltered
10. customAfter removal of the solvent under vacuum an oil (about 110 g)
11. customis obtained
12. customThe solution is degassed
13. additiondiethyl(3-pyridyl)borane (54.5 g), bis(triphenylphosphine)palladium II chloride (1.8 g) and a 2M sodium carbonate aqueous solution (500 mL) are added in sequence in an inert gas environment
14. temperatureThe resulting mixture is refluxed for about 1 h
15. additionethyl acetate (1 L) and water (1 L) are added
16. extractionThe aqueous phase is back-extracted with ethyl acetate (0.5 L)
17. concentrationthe combined organic phases are concentrated under vacuum