反应详情

A clear colorless solution of 5-bromo-1-methyl-1H-imidazole (1.12 g, 6.93 mmol) in THF (10 mL) was placed in an ice bath and ethylmagnesium bromide (3.0 M in Et2O, 2.31 mL, 6.93 mmol) was added via syringe. The reaction mixture was stirred for 20 minutes at room temperature. N-Methoxy-N-methyltetrahydro-2H-pyran-4-carboxamide (1.0 g, 5.8 mmol, Intermediate 1: step a, Procedure A) was added neat by syringe (using 1 mL THF rinse to quantitate transfer), and the resulting white suspension was stirred at room temperature for 2 days. The mixture was diluted with saturated aqueous NH4Cl followed by water, then was extracted with EtOAc (3×). The organic phase was dried (Na2SO4), filtered, and concentrated to dryness. The crude product was purified by flash column chromatography two times (1-4% MeOH-DCM first column; 40-60% CH3CN-DCM second column) to provide the title compound as a white crystalline solid.

1. wash(using 1 mL THF rinse to quantitate transfer)
2. stirringthe resulting white suspension was stirred at room temperature for 2 days
3. additionThe mixture was diluted with saturated aqueous NH4Cl
4. extractionwas extracted with EtOAc (3×)
5. dry with materialThe organic phase was dried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated to dryness
8. customThe crude product was purified by flash column chromatography two times (1-4% MeOH-DCM first column; 40-60% CH3CN-DCM second column)