1,4-Dioxane → Ethyl 3,5-diethylpyridine-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of ethyl 3,5-dibromopyridine-4-carboxylate (5.98 g, 19.35 mmol) in anhydrous dioxane (40 mL) was added at room temperature (1,1′-bis(diphenylphosphino)ferrocene)dichloropalladium (II) (424 mg, 0.580 mmol). Diethylzinc (3.58 g, 23.8 mL, 28.95 mmol, 15% solution in toluene) was then added dropwise. The reaction mixture was heated at 70° C. for 45 minutes, then cooled to room temperature and quenched with MeOH. The resulting mixture was extracted with ethyl acetate (2×100 mL), washed with water, 0.1 N HCl, and brine. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated, and the residue was purified by CombiFlash using 0-30% ethyl acetate in hexane to provide ethyl 3,5-diethylpyridine-4-carboxylate as a pale yellow oil (2.2 g, 54.8% yield); 1H NMR (400 MHz, CDCl3): δ 1.23 (t, 6H), 1.40 (t, 3H), 2.64 (q, 4H), 4.44 (q, 2H), 8.36 (s, 2H), M+208.5; M+180.2.

Provenance & Evidence