反应详情

A solution of 7-bromo-5-fluoro-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-4-[(phenylmethyl)oxy]-1H-indole (D6) (400 mg, 0.769 mmol) in toluene (10 mL) was degassed by bubbling Argon through for a few minutes and tributylstannane (0.248 mL, 0.922 mmol) was added. The mixture was heated to reflux under argon and AIBN (˜5 mg) was added and refluxing was continued. After 6 hours, another 0.124 mL of Bu3SnH and a few crystals of AIBN were added and the mixture refluxed overnight—only a small amount of further reaction occurred therefore another 0.124 mL of Bu3SnH and a few crystals of AIBN added and refluxing continued, again further reaction occurred but then stopped. Further quantities of Bu3SnH (4×0.124 mL) together with a few crystals of AIBN were added at approx 2 hourly intervals. It was noticed that the reaction proceeded much more with thorough degassing with argon prior to addition of Bu3SnH. After completion of the reaction (˜48 hours total reaction), the toluene was evaporated and ether/20% aqueous ammonia were added. The product was extracted into ether and the extracts were washed with 20% aqueous ammonia (3×). The ether layer was dried over Na2SO4 and concentrated and the product was triturated with hexane to remove high Rf impurities. Chromatography on silica gel (elution with 0-15% diethyl ether in hexane) gave the title compound as a clear gum (D7), (143 mg).

1. additionwas added
2. temperatureThe mixture was heated
3. temperatureto reflux under argon
4. temperaturerefluxing
5. temperaturethe mixture refluxed overnight—only
6. customa small amount of further reaction
7. temperaturerefluxing
8. customagain further reaction
9. customwith thorough degassing with argon
10. additionto addition of Bu3SnH
11. customAfter completion of the reaction (˜48 hours total reaction)
12. customthe toluene was evaporated
13. additionether/20% aqueous ammonia were added
14. extractionThe product was extracted into ether
15. washthe extracts were washed with 20% aqueous ammonia (3×)
16. dry with materialThe ether layer was dried over Na2SO4
17. concentrationconcentrated
18. customthe product was triturated with hexane
19. customto remove high Rf impurities