反应详情

温度

-78 °C

To a solution of 146 (10 g, 0.034 mol) in dry THF (100 mL) at −78° C. was added dropwise 1.6 M N-butyl lithium solution in hexane (23 mL, 0.0374 mol). After stirring for 45 min at −78° C., a solution of DMF (5 g, 0.068 mol) in THF (20 mL) was added dropwise. After 1 h at −78° C. the reaction mixture was quenched slowly by adding water. The aqueous phase separated was extracted with EtOAc and the combined organic extracts washed with water and brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with 15% EtOAc/petroleum ether to afford 7.7 g (93%) of 4-fluoro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole-5-carbaldehyde (148) as a yellow solid.

1. customAfter 1 h at −78° C. the reaction mixture was quenched slowly
2. additionby adding water
3. customThe aqueous phase separated
4. extractionwas extracted with EtOAc
5. washthe combined organic extracts washed with water and brine
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude product was purified by SiO2 chromatography
10. washeluting with 15% EtOAc/petroleum ether