The Synthesis Of Cbz-cyclohexyl-L-glycine

In this paper,hydrogenation and amino-protected were carried within L-phenyl glycine and benzyl chloroformate as raw material to obtained the Cbz-Cyclohexyl-L-glycine.There are two parts as following:Firstly,the hydrogenation was carried on L-Phenyl glycine with 5% Rh/C to obtain the L-cyclohexylglycine.We optimized the current process that the L-cyclohexylglycine was separated from the hydrogenation liquid to avoid the negative effects for the next amino protective reaction.Base on the optimized process,a few factors had been considered which affected the yield,such as the hydrogenation temperature,pressure and p H value.According to the single factor experiments and orthogonal experiments result,optimum condition had been achieved: the hydrogenation temperature of 80?,pressure of 1.5MPa and p H value of 7 after filtration.The sample had been examined by the melting point and the thin layer chromatography,and the purity was had been tested by HPLC.The optimum process had been verified by the pilot production and the yield was 87.14%.Serial experiments began with the synthesis of Cbz-Cyclohexyl-L-glycine which was processed from L-cyclohexylglycine and benzyl chloroformate under alkaline environment.We optimized the current process that the quantity of organic solvent and the waste were reduced,the yield was raised and the cost of raw material was reduced.Base on the optimized process,a few factors had been considered which affected the yield,such as temperature,p H value and molar ratio of reactant.According to the single factor experiments and orthogonal experiments result,optimum condition had been achieved: the reaction temperature of 0?,p H value of 14,n(benzyl chloroformate): n(L-Phenyl glycine)=1.2:1.0.The sample had been examined by the melting point,and the product was characterized by infrared spectroscopy and NMR to prove that the composition of the product was Cbz-Cyclohexyl-L-glycine.And the purity was had been tested by HPLC.The optimum process had been verified by the pilot production and the yield was 82.93%.