3-硝基吡咯烷-1-羧酸叔丁基酯的合成

Synthesis of 3-nitropyrrolian-1-carboxylate tert-butyl ester

以1-Boc-3-吡咯烷酮为原料(2),与盐酸羟胺发生羟肟化反应生成1-Boc-3-吡咯烷酮肟(3),再经氧化反应得到3-硝基吡咯烷-1-羧酸叔丁基酯(1),终产物经柱层析纯化,结构经1H NMR和LC-MS表征确证。优化了反应条件:第一步的羟肟化反应中,物料比为n盐酸羟胺∶n1-Boc-3-吡咯烷酮=1.1∶1,反应温度60℃;第二步氧化反应中,物料比为nUHP∶n3=2.5∶1,溶剂用乙腈,反应温度80℃。在优化条件下,肟化反应的最高收率达98.5%,氧化反应收率可达60%,总收率59.1%。此法合成途径简捷、条件温和、产品质量好、总收率高。

1-Boc-3-pyrrolidone oxime(2) was reacted with hydroxylamine to produce 1-Boc-3-pyrrolidone oxime(3),which was then oxidized to obtain 3-nitropyrrolian-1-carboxylate tert-butyl ester(1).The final product was purified by column chromatography,and the structure was confirmed by 1 H NMR and LC-MS.The reaction conditions were optimized as follows:in the first step of hydroxime reaction,the material ratio was nhydroxylarnine hydrochloride:n1-Boc--3-pymolidone=1.1:1,and the reaction temperature was 60℃.In the second step of oxidation reaction,the material ratio is nUHP:n3=2.5:1,the solvent is acetonitrile,and the reaction temperature is 80℃.Under the optimized conditions,the maximum yield of hydroxime reaction is 98.5%,oxidation reaction is 60%,and total yield is 59.1%.This method has the advantages of simple synthesis,mild conditions,good product quality and high total yield.