反应详情

A solution of n-BuLi (3.8 mL, 9.5 mmol, 2.5 M solution in hexane) was added slowly to a solution of 1-methyl-1H-1,2,3-triazole (0.83 g, 10 mmol) in THF (48 mL) at −50° C. After addition, stirring was continued for an additional 30 minutes and N-methoxy-N,2,6-trimethylisonicotinamide (0.97 g, 5.0 mmol, Intermediate 29: step a) dissolved in THF (12 mL) was slowly added. An additional 2 mL of THF was used to complete the quantitative addition. The mixture was stirred at −50° C. for 5 minutes then warmed to room temperature and stirred overnight. The solution was quenched with saturated aqueous NH4Cl. H2O was added and layers were separated. The aqueous layer was extracted with EtOAc and the combined organic extracts washed with brine, dried over MgSO4, filtered and evaporated in vacuo. The crude product was purified using flash column chromatography (0 to 100% EtOAc/DCM) to provide the title compound.

1. additionAfter addition
2. additionwas slowly added
3. additionthe quantitative addition
4. stirringThe mixture was stirred at −50° C. for 5 minutes
5. stirringstirred overnight
6. customThe solution was quenched with saturated aqueous NH4Cl
7. additionH2O was added
8. customlayers were separated
9. extractionThe aqueous layer was extracted with EtOAc
10. washthe combined organic extracts washed with brine
11. dry with materialdried over MgSO4
12. filtrationfiltered
13. customevaporated in vacuo
14. customThe crude product was purified