反应详情

温度

80 °C

Compound 196 (0.178 g, 0.521 mmol), compound 194 (0.125 g, 0.434 mmol), and LiHMDS 1M in THF (1.30 mL, 1.30 mmol) were combined in 5 mL of anhydrous toluene. N2 was bubbled through the solution briefly before adding Pd2(dba)3 (0.0298 g, 0.0326 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (0.0377 g, 0.0652 mmol). The solution was then heated to 80° C. for 2 hours with microwave irradiation. The solution was diluted with DCM before it was poured into sat's NH4Cl. Partitioned the layers and washed the aqueous layer with 10% i-PrOH/DCM. The combined organics were dried over MgSO4 and then concentrated under vacuum. The residue obtained was purified on CombiFlash column (dry loaded), eluting with a gradient of 60% ethyl acetate/hexane to 100% ethyl acetate. The fractions containing the product were combined and concentrated under vacuum. The residue obtained was repurified on CombiFlash column (dry loaded), eluting with a gradient of 2% methanol/0.1% NH4OH (˜28% in water)/DCM to 4% methanol/0.2% NH4OH (˜28% in water)/DCM. The fractions containing the product were combined and concentrated under vacuum. The residue obtained was sonicated in methanol. Filtration provided an off-white solid as compound 197 (0.173 g, 72%). LCMS-ESI (POS), M/Z, M+1: Found 549.1.

1. customN2 was bubbled through the solution briefly
2. customPartitioned the layers
3. washwashed the aqueous layer with 10% i-PrOH/DCM
4. dry with materialThe combined organics were dried over MgSO4
5. concentrationconcentrated under vacuum
6. customThe residue obtained
7. customwas purified on CombiFlash column (dry loaded)
8. washeluting with a gradient of 60% ethyl acetate/hexane to 100% ethyl acetate
9. additionThe fractions containing the product
10. concentrationconcentrated under vacuum
11. customThe residue obtained
12. customwas repurified on CombiFlash column (dry loaded)
13. washeluting with a gradient of 2% methanol/0.1% NH4OH (˜28% in water)/DCM to 4% methanol/0.2% NH4OH (˜28% in water)/DCM
14. additionThe fractions containing the product
15. concentrationconcentrated under vacuum
16. customThe residue obtained
17. filtrationFiltration