2,6-Dimethylnicotinaldehyde → (4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)methanol

Participants

Reaction Conditions

Reaction Steps

To a flask containing 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (1.85 g, 4.3 mmol, Intermediate 5: step d) was added THF (45 mL) at room temperature which resulted in a colorless homogeneous solution. The solution was cooled to −70° C. and then n-BuLi (2.5 M in hexanes, 1.75 mL, 4.38 mmol) was added dropwise. After 2 minutes, 2,6-dimethylnicotinaldehyde (755 mg, 5.50 mmol, in 2 mL THF) was introduced and the color of the mixture changed from a reddish-brown to green. The reaction mixture was allowed to warm to −20° C. over 40 minutes at which time the reaction was quenched with aqueous NH4Cl solution. The aqueous portion was extracted with EtOAc (3×50 mL) and the combined organics were washed with brine, dried over MgSO4, filtered and concentrated to dryness. Chromatography on silica gel (10% acetone-hexane increasing to 30% acetone) afforded the title compound.

Provenance & Evidence