左旋烟碱的合成研究

Synthesis of L-Nicotine

以3-溴吡啶及异丙基氯化镁为起始原料进行反应制备3-溴吡啶的格氏试剂,在手性催化剂的催化下与3,4-二氢-2H-吡咯偶联获得手性中间体,再与碘甲烷反应获得左旋烟碱,通过HPLC、NMR对合成的目标产物进行了表征和确证,并对合成路线进行了优化,最优路线:3-溴吡啶(1.0 eq.),异丙基氯化镁(1.2 eq.),手性催化剂(0.005 eq.),3,4-二氢-2H-吡咯(1.2 eq.),碳酸钾(2.0 eq.),碘甲烷(1.1 eq.),反应温度25oC,反应时间12 h,左旋烟碱产率为78.2%。

3-Pyridyl bromide grignard reagent was prepared by 3-pyridyl bromide and isopropylmagnesium chloride.React-ed with Ir-catalyst,3,4-dihydro-2H-pyrrole coupling with 3-pyridyl bromide grignard reagent,and then reacted with io-domethane to synthesis L-nicotine.L-nicotine was characterized by HPLC and NMR.At the same time,optimized the syn-thetic route,and the optimized result were 3-pyridyl bromide(1.0 eq.),isopropylmagnesium chloride(1.2 eq.),Ir-cata-lyst(0.005 eq.),3,4-dihydro-2H-pyrrole(1.2 eq.),potassium carbonate(2.0 eq.),iodomethane(1.1 eq.),reaction temperature 25oC and reaction time 12 h,the yield was 78.2%.