反应详情

温度

82.5 °C

Triethylamine (33 mg, 0.33 mmol) and tert-butyl acrylate (77 mg, 0.6 mmol) followed by diphenylpropylphosphine (3.4 mg, 0.008 mmol) and palladium(II) acetate (1.7 mg, 0.0075 mmol) were added to a solution of 4-(4-chloro-2-fluorophenoxy)-6-methoxy-7-(trifluoromethylsulphonyloxy)quinazoline (136 mg, 0.3 mmol) in DMF (1.5 ml) under argon. When the addition was complete the reaction flask was purged with argon. The mixture was stirred at 80-85° C. for 6 hours. After cooling, the mixture was partitioned between ethyl acetate and water. The aqueous layer was adjusted to pH6 with 2M hydrochloric acid. The organic layer was separated, washed with water, brine, dried (MgSO4) and evaporated. The residue was purified by column chromatography eluting with methylene chloride followed by methylene chloride/ether (95/5). After removal of the solvent under vacuum, the solid was triturated with pentane/ether, collected by filtration and dried under vacuum to give 4-(4-chloro-2-fluorophenoxy)-6-methoxy-7-(2-(tert-butoxycarbonyl)vinyl)quinazoline (63 mg, 49%).

1. additionWhen the addition
2. customwas purged with argon
3. temperatureAfter cooling
4. customthe mixture was partitioned between ethyl acetate and water
5. customThe organic layer was separated
6. washwashed with water, brine
7. dry with materialdried (MgSO4)
8. customevaporated
9. customThe residue was purified by column chromatography
10. washeluting with methylene chloride
11. customAfter removal of the solvent under vacuum
12. customthe solid was triturated with pentane/ether
13. filtrationcollected by filtration
14. customdried under vacuum