反应详情

To a cooled solution (−78° C.) of 2-(2-benzyloxy-ethyl)-3-bromo-benzo[b]thiophene (9.6 g, 27.6 mmol) in anhydrous THF (200 mL), TMEDA (4.14 mL, 27.6 mmol) was added and the mixture was stirred for 5 min. After dropwise addition of sec-BuLi (23.3 mL, 30.3 mmol), while keeping the temperature below −60° C., the mixture was stirred for an additional 30 min at −78° C. A solution of 2-cyanopyridine (3.16 g, 30.34 mmol) in toluene (30 mL) was added and after stirring for 30 min at −78° C. the reaction was quenched by dropwise addition of 6N HCl (66 mL) in MeOH (134 mL), while keeping the temperature below −60° C. After stirring overnight while allowing the mixture to reach room temperature, the mixture was concentrated in vacuo. The residue was dissolved in dichloromethane (100 mL) and NH4OH (100 mL) was added. The organic layer was separated and the aqueous layer was further extracted with dichloromethane. The combined organic layers were dried (Na2SO4), concentrated and subjected to silica gel column chromatography (eluent: EtOAc/Hex=1/4 up to EtOAc/Hex=1/1) to afford 4.2 g of [2-(2-benzyloxy-ethyl)-benzo[b]thiophen-3-yl]-pyridin-2-yl-methanone (41% yield).

1. customthe temperature below −60° C.
2. stirringthe mixture was stirred for an additional 30 min at −78° C
3. stirringafter stirring for 30 min at −78° C. the reaction
4. customwas quenched by dropwise addition of 6N HCl (66 mL) in MeOH (134 mL)
5. customthe temperature below −60° C
6. stirringAfter stirring overnight
7. customto reach room temperature
8. concentrationthe mixture was concentrated in vacuo
9. dissolutionThe residue was dissolved in dichloromethane (100 mL)
10. additionNH4OH (100 mL) was added
11. customThe organic layer was separated
12. extractionthe aqueous layer was further extracted with dichloromethane
13. dry with materialThe combined organic layers were dried (Na2SO4)
14. concentrationconcentrated