1,2-dimethyl-1H-imidazole-5-carbaldehyde → (4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanol

Temperatur

-70 °C

To a 50 mL flask containing 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (2 g, 4.64 mmol, Intermediate 47: step d) was added THF (25 mL) at room temperature which resulted in a colorless homogeneous mixture. The solution was cooled to −70° C. which remained homogeneous and then n-BuLi (2.5 M in hexanes, 1.8 mL, 4.5 mmol) was added drop wise. The color of the solution became a dark reddish-brown color. After 1 minute, 1,2-dimethyl-1H-imidazole-5-carbaldehyde (710 mg, 5.72 mmol in 4 mL THF) was introduced and the color of the mixture became greenish to light orange all within 1 minute. The mixture was allowed to warm to 0° C. over 45 minutes at which time the reaction was quenched with aqueous NH4Cl solution. The reaction was diluted further with water and extracted with EtOAc (3×45 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to give a pale yellow solid. The solid was triturated with Et2O and collected by filtration and rinsed with additional Et2O and dried to afford the title compound as a white powder.

1. customresulted in a colorless homogeneous mixture
2. customwithin 1 minute
3. temperatureto warm to 0° C. over 45 minutes at which time the reaction
4. customwas quenched with aqueous NH4Cl solution
5. additionThe reaction was diluted further with water
6. extractionextracted with EtOAc (3×45 mL)
7. washThe combined organics were washed with brine
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customto give a pale yellow solid
12. customThe solid was triturated with Et2O
13. filtrationcollected by filtration
14. washrinsed with additional Et2O
15. customdried

ORD-Eintrag

ord-4026698472d94e7499a81186908465f6

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09290476B2