反应详情

A solution of n-BuLi (4.0 mL, 10 mmol, 2.5 M solution in hexane) was slowly added to a solution of 5-bromo-1,2-dimethyl-1H-imidazole (1.77 g, 10.2 mmol) in THF (70 mL) at −78° C. After addition, stirring was continued for an additional 30 minutes and N-methoxy-N-methyltetrahydro-2H-pyran-4-carboxamide (1.76 g, 10.1 mmol, Intermediate 1: step a, Procedure A) dissolved in THF (25 mL) was slowly added. An additional 6 mL of THF was used to complete the quantitative addition. The mixture was stirred at −78° C. for 5 minutes then warmed to room temperature and stirred for 1 hour. The solution was quenched with water and layers were separated. The aqueous layer was extracted with DCM 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 6% MeOH/DCM) to provide the title compound.

1. additionAfter addition
2. additionwas slowly added
3. additionthe quantitative addition
4. stirringThe mixture was stirred at −78° C. for 5 minutes
5. stirringstirred for 1 hour
6. customThe solution was quenched with water and layers
7. customwere separated
8. extractionThe aqueous layer was extracted with DCM
9. washthe combined organic extracts washed with brine
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. customevaporated in vacuo
13. customThe crude product was purified