4-Methylpyridine → HCID 67258297, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-methylpyridine (1 eq, 75 mmol) in anhydrous THF (50 mL) was added n-butyl lithium 2.5 M solution (1.3 eq, 98 mmol) at −50° C. under nitrogen. The reaction mixture was stirred for 30 min at −50° C. To the mixture was slowly added a solution of methyl 3-chloro-2-thiophenecarboxylate (1 eq, 75 mmol, synthesis described in Heterocycles, 2007, 71(1), 87) in anhydrous THF (50 mL) at −50° C. The reaction mixture was stirred at −50° C. for 30 min, then allowed to warm to room temperature and stirred for 2 h. The mixture was quenched with aqueous saturated ammonium chloride solution (150 mL). The organic layer was separated and the aqueous phase was extracted with ethyl acetate (3×100 mL). The combined extracts were washed with water, brine, dried over Na2SO4 and concentrated. The obtained dark brown residue was purified by column chromatography on silica gel (DCM:MeOH, 100:1 to 80:1) to afford 4 g of 1-(3-chloro-2-thienyl)-2-(pyridin-4-yl)ethanone (22% yield).

Provenance & Evidence