反应详情

THF was dried over 3A molecular sieves prior to use. To a stirred suspension of epothilone F (10 g, 19.1 mmol) in dry tetrahydrofuran (200 ml) under argon, was added diphenylphosphoryl azide (6.20 ml, 7.90 g, 28.6 mmol, 1.5 equivalents). The mixture was stirred for about 10 min. 1,8-diazabicyclo[5.4.0]undec-7-ene (3.43 ml, 3.53 g, 22.8 mmol, 1.2 equivalents) was added gradually, at a rate that maintained the temperature of the mixture below 30° C. The mixture was stirred for 12 to 24 hours (overnight). To the reaction mixture was added a solution of 1.0 M trimethylphosphine in tetrahydrofuran (21 ml, 18.3 g, 21.04 mmol, 1.1 equivalents), at a rate that maintained the temperature of the mixture below 27° C. The mixture was stirred at room temperature for 30 minutes, and water (52 ml) was added. After 30 minutes, 28% aqueous NH4OH (26.5 ml) was added, and the mixture stirred for 30 minutes. Water (100 ml) was added, and the mixture was extracted with methylene chloride (3×100 ml). The combined organic extracts were washed with 1.0M aqueous ammonium hydroxide (2×100 ml). NMR analysis was used to determine the presence of residual diphenylphosphate in the organic phase, and an additional wash with 1.0 M aqueous ammonium hydroxide (100 ml) was carried out. The organic phase was then washed with half-saturated aqueous sodium chloride (100 ml), the solvents were removed on a rotary evaporator, and the residual solid was dried in vacuo for 18 hours. The crude product was purified within 24 hours, or stored at −15° C. or below.

1. dry with materialTHF was dried over 3A molecular sieves
2. temperaturemaintained the temperature of the mixture below 30° C
3. stirringThe mixture was stirred for 12 to 24 hours (overnight)
4. temperatureat a rate that maintained the temperature of the mixture below 27° C
5. stirringThe mixture was stirred at room temperature for 30 minutes
6. waitAfter 30 minutes
7. stirringthe mixture stirred for 30 minutes
8. extractionthe mixture was extracted with methylene chloride (3×100 ml)
9. washThe combined organic extracts were washed with 1.0M aqueous ammonium hydroxide (2×100 ml)
10. washan additional wash with 1.0 M aqueous ammonium hydroxide (100 ml)
11. washThe organic phase was then washed with half-saturated aqueous sodium chloride (100 ml)
12. customthe solvents were removed on a rotary evaporator
13. customthe residual solid was dried in vacuo for 18 hours
14. customThe crude product was purified within 24 hours
15. customstored at −15° C. or below