Abstract: New process reported the synthesis of telavancin using decyl alcohol as the starting material. After methanesulfonylation, nucleophilic substitution with ethanolamine, Fmoc protection, and Parikh-Doering oxidation, the intermdiate N-(9-fluorenyl-9-methoxycarbonyl)decylaminoethyl acetaldehyde( 5 )was obtained. Vancomycin hydrochloride and intermediate 5 were then subject to reductive amination reaction, Fmoc deprotection, and Mannich reaction to give the telavancin product. The process have been deeply studied on the two key reactions of reductive amination and Mannich reaction, and the reaction conditions have been optimized. The overall yield is 46% based on starting material vancomycin.