反应详情

温度

55 °C

To an ice cold solution of Intermediate 139a (574 mg, 2.26 mmol) in THF (23.0 mL) was added sequentially triphenylphosphine (1.18 g, 4.52 mmol), triethylamine (1.26 mL, 9.04 mmol) and hexachloroethane (1.07 g, 4.52 mmol). The cooling bath was removed and the reaction was heated to 55° C. overnight. The reaction was cooled and partitioned between EtOAc and water. The aqueous layer was then extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was taken up in MeOH and loaded onto an SCX-2 cartridge, which was washed with MeOH and eluted with 2M NH3 in MeOH. The residue was concentrated in vacuo and then re-submitted to the above reaction conditions overnight. The reaction was cooled and partitioned between EtOAc and water. The aqueous layer was then extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was purified by FCC using 0-10% [2M NH3 in MeOH] in DCM to give the title compound (154 mg, 29%). 1H NMR (300 MHz, CDCl3): 0.94 (3H, d, J=6.3 Hz), 3.13 (1H, dt, J=12.2, 3.1 Hz), 3.32 (1H, ddd, J=12.4, 9.5, 3.2 Hz), 3.49 (1H, dd, J=11.1, 8.6 Hz), 3.56-3.68 (1H, m), 3.84 (1H, ddd, J=12.1, 9.4, 2.7 Hz), 3.92-4.01 (2H, m), 7.16 (1H, ddd, J=9.9, 7.5, 2.3 Hz), 7.68 (1H, ddd, J=10.0, 4.8, 0.8 Hz), 7.85 (1H, m).

1. customThe cooling bath was removed
2. temperatureThe reaction was cooled
3. custompartitioned between EtOAc and water
4. extractionThe aqueous layer was then extracted with EtOAc (3×)
5. washThe combined organic layers were washed with brine
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. customevaporated in vacuo
9. washwas washed with MeOH
10. washeluted with 2M NH3 in MeOH
11. concentrationThe residue was concentrated in vacuo
12. customre-submitted to the above reaction conditions overnight
13. temperatureThe reaction was cooled
14. custompartitioned between EtOAc and water
15. extractionThe aqueous layer was then extracted with EtOAc (3×)
16. washThe combined organic layers were washed with brine
17. dry with materialdried (MgSO4)
18. filtrationfiltered
19. customevaporated in vacuo
20. customThe residue was purified by FCC