Lithium diisopropylamide → Racemic 1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2,2-dipyridin-3-ylethanol

Participants

Reaction Conditions

Reaction Steps

A solution of 3,3′-methylenedipyridine (340 mg, 1.99 mmol) in THF (20 mL) at −78° C. was treated with lithium diisopropylamide (2.65 mL of a 1.5 M solution of the mono-THF complex in cyclohexane, 3.98 mmol) dropwise. After stirring at −78° C. for 30 min, 2-(3,5-dichlorophenyl)nicotinaldehyde (500 mg as a solution in 6 mL THF, 1.99 mmol) was added dropwise via syringe. The reaction mixture was stirred for 1 h at −78° C., warmed to 0° C. over 5 min, then quenched with the addition of 100 mL H2O. The mixture was extracted with EtOAc (3×60 mL) and organic extracts were pooled, dried (Na2SO4), concentrated under reduced pressure, and purified by flash chromatography (40 g SiO2, 0-10% MeOH/CH2Cl2 gradient elution) to provide racemic 1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2,2-dipyridin-3-ylethanol. Resolution was performed by HPLC using a chiral stationary phase (ChiralPak AD, 5 cm×50 cm, 20μ, 40-100% i-PrOH/hexanes gradient elution modified with 1 mL/L diethylamine, 80 mL/min) and provided the title compound.

Provenance & Evidence