Acetic Acid → Ethyl 3-(3,5-dibromopyridin-4-yl)propanoate

Participants

Reaction Conditions

Reaction Steps

To a solution of LDA (0.308 mol) [generated from N,N-diisopropylamine (31.2 g, 0.308 mol) and n-BuLi (123 mL, 0.308 mol, 2.5M in hexane) in 800 mL THF] was added slowly a solution of 3,5-dibromo-4-methylpyridine (70 g, 0.28 mol) in THF (300 mL) while the inner temperature was maintained below −70° C. After the addition, the resulting mixture was stirred for another 30 min at −78° C. before ethyl bromoacetate (116.9 g, 0.7 mol) was slowly added and the reaction mixture was stirred at −78° C. for another 1.5 h. 10% aq. AcOH was added (resulting pH=4-5), and the reaction was allowed to warm up to room temperature. After evaporation of solvent, the residue was poured into sat. aq. NaHCO3 solution, and was extracted with EtOAc (1 L×3). The combined organic layers were washed with brine and dried over Na2SO4, filtered and concentrated in vacuo to give a crude product which was purified by column chromatography (n-pentane:EtOAc=15:1˜5:1) to afford the title compound (30 g, 32%) as a gray solid. MS: 337.7 (M+H+, 2 Br).

Provenance & Evidence