Suvorexant关键中间体的合成研究

Synthesis of the Key Intermediate of Suvorexant

以2-氨基乙醇(2)为原料,经Ns保护,与(R)-(3-羟丁基)-氨基甲酸叔丁酯(4)发生缩合反应,再经Mitsunobu关环与脱Ns保护反应,得到Suvorexant关键中间体1。总收率为57%,产物的结构经~1H NMR和MS分析确证,该方法操作简单、收率高、无手性异构体杂质产生。

（R）-Tert-butyl 5-methyl-1,4-diazepane-1-carboxylate （1）, a key intermediate for Suvorexant was synthesized via N-protection using 2-aminoethanol （2） as the staring material, followed by condensation with （R）- tert-butyl （3-hydroxybutyl）carbamate （4）, which finally led to 1 through Mitsunobu and deprotection reactions. The total yield was up to 57%, and the structure of the product was characterized using 1H NMR and MS spectra. The improved synthetic route was of advantages including simple operation, high yield, and none of chiral isomers impurity production.