反应详情

温度

45 °C

A solution of Intermediate 55e (710 mg, 2.17 mmol), Intermediate C (385 mg, 2.17 mmol) and DIPEA (250 μL, 3.25 mmol) in 1,4-dioxane (10 mL) was stirred at 60° C. overnight. After cooling, the mixture was partitioned between EtOAc and water. The aqueous layer was then extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo to give a gum (1.25 g, quantitative) that was used without further purification in the next step. TLC [DCM/MeOH (9:1) Rf=0.4]. A solution of the above product (1.25 g, 1.30 mmol) in MeOH (30 mL) was treated with pyridinium p-toluenesulfonate (978 mg, 3.90 mmol) and the resulting mixture was heated at 45° C. overnight. The volatiles were removed under reduced pressure and the residue was taken up in DCM (80 mL) and washed with water (20 mL). The organic phase was separated using a phase separating cartridge and the organic layer was evaporated in vacuo. The product was purified by FCC, eluting with 0-10% MeOH in DCM, to give the title compound (430 mg, 40%). LCMS (Method 3): Rt 5.41 min, m/z 879,880 [MH+].

1. temperatureAfter cooling
2. customthe mixture was partitioned between EtOAc and water
3. extractionThe aqueous layer was then extracted with EtOAc (3×10 mL)
4. washThe combined organic layers were washed with brine
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. customevaporated in vacuo
8. customto give a gum (1.25 g, quantitative) that
9. customwas used without further purification in the next step
10. customThe volatiles were removed under reduced pressure
11. washwashed with water (20 mL)
12. customThe organic phase was separated
13. customseparating cartridge
14. customthe organic layer was evaporated in vacuo
15. customThe product was purified by FCC
16. washeluting with 0-10% MeOH in DCM