吉米沙星关键中间体4-氨甲基吡咯烷-3-酮-O-甲基肟二盐酸盐的合成方法改进

Improved synthesis of a gemifloxacin intermediate 4-(aminomethyl)pyrrolidin-3-one-O-methyloxime dihydrochloride

目的合成抗菌药吉米沙星关键中间体4-氨甲基吡咯烷-3-酮-O-甲基肟二盐酸盐。方法以甘氨酸乙酯盐酸盐为原料,依次经加成、Boc保护氨基、Dieckmann环化、NaBH4还原羰基、LiAlH4还原氰基、Boc保护氨甲基、氧化、肟化、脱Boc保护等9步反应制得目标化合物。结果与结论合成的目标化合物经1H-NMR和MS谱确证结构,总收率由25.8%提高至39.6%。该合成工艺省去了文献方法中对中间体4和6的柱色谱分离,不经纯化直接用于下步反应,简化了操作步骤。

Aim To synthesize a gemifloxacin intermediate,4-（aminomethyl） pyrrolidin-3-one-O-methyloxime dihydrochloride. Methods Commercially available glycine ethyl ester hydrochloride was used as starting material to give the target compound via addition, protection with Boc, Dieckmann cyclization, reduction with NaBH4 and LiAlH4, protection, oxidation, oximation and deprotection. Results and conclusion The target compound was prepared in 39.6% overall yield and its structure was identified by ^1H-NMR and MS.