反应详情

To a flask containing 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (Intermediate 12: step d, 3.0 g, 6.97 mmol) was added THF (40 ml) and the solution was cooled to −70° C. n-BuLi (2.5 M in hexanes, 2.8 mL, 7 mmol) was added dropwise. After 2 minutes, 1-methyl-1H-imidazole-5-carbaldehyde (1.2 g, 9 mmol, in 10 mL THF) was introduced. After 15 minutes, the dry-ice bath was replaced with a 0° C. bath. After 35 minutes the reaction mixture was quenched with aqueous NH4Cl solution and the aqueous portion was extracted with EtOAc:THF (10:2) 5×50 mL. The combined organics were washed with brine, dried over Na2SO4, filtered and concentrated to dryness to give the title compound.

1. additionwas added dropwise
2. waitAfter 15 minutes
3. customwas replaced with a 0° C.
4. customAfter 35 minutes the reaction mixture was quenched with aqueous NH4Cl solution
5. extractionthe aqueous portion was extracted with EtOAc:THF (10:2) 5×50 mL
6. washThe combined organics were washed with brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated to dryness