Diisopropylamine → 2-Chloro-alpha-(3-methoxyphenyl)-3-pyridinemethanol

Participants

Reaction Steps

Combine 2.5 M n-butyl lithium in hexane (40 mL), diisopropyl amine (14 mL, 0.10 mol) and cold (−68° C.) tetrahydrofuran (250 mL) and stir for 20 minutes, to generate lithium diisopropylamide. Add 2-chloro-pyridine (9.5 mL, 0.10 mol) dissolved in tetrahydrofuran (10 mL) and stir for 45 minutes. Add m-anisaldehyde (13.6 g, 0.10 mol) in 10 mL tetrahydrofuran, stir for 45 minutes and let warm to room temperature over the weekend. Pour reaction mixture into water, add saturated ammonium chloride (50 mL), separate and dry. Extract with ether (twice), wash combined aqueous layers with saturated sodium chloride, dry, evaporate and purify by flash (silica) chromatography using a graded solvent mixture of dichloromethane to 10% ethyl acetate in dichloromethane to give the title compound as an oil (12.74 g, 51% Yield). NMR agrees with the final, desired compound.

Provenance & Evidence