反应详情

温度

95 °C

A 12 L flask was charged with 2-[2-bromo-5-(tert-butyl-dimethyl-silanyloxy)-benzyl]-isoindole-1,3-dione (461 g, 1.03 mol), propionitrile (7 L), tri-ortho-tolyl phosphine (76.0 g, 0.250 mol) and diisopropyl ethyl amine (365 mL, 2.10 mol). The reaction mixture was degassed/purged with N2 (3×), and tert-butyl acrylate (465 mL, 3.17 mol) was added. After degassing/purging one time, palladium (II) acetate (28.0 g, 0.125 mol) was added. The stirred mixture was degassed/purged with N2 three times and heated to 95° C. for 20 h. The mixture was filtered through a hyflo cake, washed with acetonitrile, and concentrated to a brown oil (841 g). The residue was dissolved in THF (3.5 L), and tetrabutylammonium fluoride (TBAF, 650 mL, 0.65 mol, 1M in THF) was added. After 1 h, additional TBAF (95 mL) was added. The mixture was rotated on the rotary evaporator for 10 min and was concentrated to crude product (987 g). This material was purified by silica gel chromatography (toluene/ethyl acetate, 100/0 to 75/25) to give the title compound (340 g, 86.8%).

1. additionwas added
2. additionwas added
3. customThe stirred mixture was degassed/purged with N2 three times
4. filtrationThe mixture was filtered through a hyflo cake
5. washwashed with acetonitrile
6. concentrationconcentrated to a brown oil (841 g)
7. dissolutionThe residue was dissolved in THF (3.5 L)
8. customThe mixture was rotated on the rotary evaporator for 10 min
9. concentrationwas concentrated to crude product (987 g)
10. customThis material was purified by silica gel chromatography (toluene/ethyl acetate, 100/0 to 75/25)