(R)-3-羟基吡咯烷的简便合成研究

Simple Synthesis of (R)-3-hydroxypyrrolidine

(R)-3-羟基吡咯烷是合成抗生素帕尼培南的重要原料,且在医药行业应用广泛。本文以L-羟基脯氨酸为原料经高温脱羧、蒸馏,制得收率为76%,GC纯度为98.6%,ee值>99%的(R)-3-羟基吡咯烷单体,得出最佳合成工艺为:L-羟基脯氨酸∶聚乙二醇-400=1 g∶3 mL,选用2-环己烯-1-酮为催化剂,反应温度160℃,反应时间10 h。其结果经质谱、核磁等进行了表征。

（R）-3-hydroxypyrrolidine is important raw material for the synthesis of antibiotics Panipenem, and iswidely used in the pharmaceutical industry. （R）-3-hydroxypyrrolidine was synthesized from L-hydroxyproline by one- step and the total yield was 76%, GC was 98.6%, ee was 99%. The optimum synthesizing process was obtained as follows： L-hydroxyproline ： Polyethylene glycol 400 = 1 g ： 3 mL, 2-cyclohexen-1-one was selected as catalyst, reaction temperature was 160 ℃, reaction time was 10 h. The structure was characterized by 1H NMR and MS.