2,6-Dimethylnicotinaldehyde → (4-Chloro-3-(4-fluorobenzyl)-2-methoxyquinolin-6-yl)(2,6-dimethylpyridin-3-yl)methanol

Participants

Reaction Steps

A solution of n-BuLi (2.5 M in hexanes, 0.84 mL, 2.1 mmol) was added dropwise by syringe to a solution of 6-bromo-4-chloro-3-(4-fluorobenzyl)-2-methoxyquinoline (0.826 g, 2.17 mmol, Intermediate 7: step d) in dry THF (11 mL) in a dry ice-acetone bath. After 1-2 minutes, a solution of 2,6-dimethylnicotinaldehyde (0.23 mL, 1.8 mmol) in dry THF (3 mL) was added dropwise. The reaction was stirred for 5 minutes, then was removed from the cold bath and allowed to warm to room temperature. The reaction was quenched with saturated aqueous ammonium chloride. The mixture was partitioned between water and dichloromethane. The separated aqueous phase was further extracted with dichloromethane. The combined organic phases were dried (Na2SO4), filtered, and concentrated. The crude product was purified by flash column chromatography (silica gel, 0-3% MeOH-DCM) to provide the title compound. 1H NMR (500 MHz, CDCl3) δ ppm 8.06 (d, J=1.9 Hz, 1H), 7.73 (d, J=8.6 Hz, 1H), 7.68 (d, J=7.9 Hz, 1H), 7.45 (dd, J=8.6, 2.0 Hz, 1H), 7.26-7.21 (m, 2H), 6.97 (d, J=7.9 Hz, 1H), 6.94-6.89 (m, 2H), 6.07 (s, 1H), 4.22 (s, 2H), 4.05 (s, 3H), 3.77 (s, 1H), 2.46 (s, 3H), 2.40 (s, 3H).

Provenance & Evidence