反应详情

A mixture of methyl 3-bromo-6-(2-bromo-4-fluorobenzenesulfonylmethyl)-2-methoxybenzoate (Intermediate 70, 5.85 g), N,N-diethyl-N-((Z)-1-tributylstannanylprop-1-en-3-yl)-amine (Intermediate 3, 5.00 g) and cesium fluoride (3.29 g) in THF (100 mL) was de-gassed and purged with nitrogen for 5 minutes. Palladium tetrakis-(triphenylphosphine) (0.720 g) was added and the reaction mixture was heated at reflux overnight. The mixture was cooled, diluted with ethyl acetate, filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica, eluting with a mixture of 2M ammonia in methanol and DCM, with a gradient of 0-10% to give methyl 3-bromo-6-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylmethyl]-2-methoxybenzoate (3.9 g) as an oil.

1. customwas de-gassed
2. custompurged with nitrogen for 5 minutes
3. additionPalladium tetrakis-(triphenylphosphine) (0.720 g) was added
4. temperaturethe reaction mixture was heated
5. temperatureat reflux overnight
6. temperatureThe mixture was cooled
7. additiondiluted with ethyl acetate
8. filtrationfiltered through Celite
9. concentrationthe filtrate was concentrated in vacuo
10. customThe residue was purified by chromatography on silica
11. washeluting with a mixture of 2M ammonia in methanol and DCM, with a gradient of 0-10%