反应详情

温度

80 °C

To compound of Step A (161.0 g, 561.8 mmol) in DMF (800 mL) is added methyl acrylate (58.0 g, 674.2 mmol), TEA (170.5 g, 1685.4 mmol) and dichlorobis(triphenylphosphine)palladium(II) (7.9 g, 11.2 mmol). The mixture is heated at 80° C. for about 32 hours. The mixture is cooled, diluted with 1000 mL of EtOAc and washed with 10% aqueous sodium bisulfate. The aqueous portion is extracted three times with EtOAc and the combined organics are dried (Na2SO4) and concentrated to dryness. The residue is dissolved in a small amount of DCM and filtered through 7 inch of silica gel in a 2 L sintered glass funnel eluting with 25% EtOAc/hexanes. The eluent is concentrated to dryness and recrystallized from EtOAc/hexanes to afford about 116.9 g (71%) of Step B compound.

1. temperatureThe mixture is cooled
2. washwashed with 10% aqueous sodium bisulfate
3. extractionThe aqueous portion is extracted three times with EtOAc
4. dry with materialthe combined organics are dried (Na2SO4)
5. concentrationconcentrated to dryness
6. dissolutionThe residue is dissolved in a small amount of DCM
7. filtrationfiltered through 7 inch of silica gel in a 2 L sintered glass funnel
8. washeluting with 25% EtOAc/hexanes
9. concentrationThe eluent is concentrated to dryness
10. customrecrystallized from EtOAc/hexanes
11. customto afford about 116.9 g (71%) of Step B compound