反应详情

温度

-70 °C

To a flask containing 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (2.0 g, 4.64 mmol, Intermediate 5: step d) was added THF (25 mL). The solution was cooled to −70° C. and then n-BuLi (2.5 M in hexanes, 1.8 mL, 4.5 mmol) was added dropwise. After 2 minutes, 1,2-dimethyl-1H-imidazole-5-carbaldehyde (720 mg, 5.8 mmol in 5 mL THF) was introduced. The reaction mixture was allowed to warm to 0° C. over 60 minutes at which time it was quenched with aqueous NH4Cl solution. The aqueous portion was extracted with EtOAc:THF (10:1, 5×50 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated. The solid was triturated with EtOAc:Et2O (1:1), collected by filtration, rinsed with additional Et2O and dried to afford the title compound. The mother liquors were concentrated and chromatographed on silica gel (3% MeOH-DCM increasing to 10% MeOH) to provide additional title compound.

1. temperatureto warm to 0° C. over 60 minutes at which time it
2. customwas quenched with aqueous NH4Cl solution
3. extractionThe aqueous portion was extracted with EtOAc:THF (10:1, 5×50 mL)
4. washThe combined organics were washed with brine
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe solid was triturated with EtOAc:Et2O (1:1)
9. filtrationcollected by filtration
10. washrinsed with additional Et2O
11. customdried