The invention provides a method for preparing a telpotide
side chain intermediate, which comprises the following steps: by taking 20-(tert-butoxy)-20-oxo-eicosanoic acid as a starting material, forming an active anhydride intermediate by using
alkyl chloroformate, adding a strong alkali solution of 1-tert-butyl L-
glutamic acid, reacting, adjusting the acid, extracting a product by using
ethyl acetate, combining organic phases, concentrating and
drying to obtain M2; taking M2 as a
raw material, forming an active anhydride intermediate by using
alkyl chloroformate, adding a strong alkali solution of AEEA-AEA, reacting, adjusting the acid, extracting a product by using
ethyl acetate, combining organic phases, concentrating, and
drying to obtain M4; and finally, taking M4 as a
raw material, forming an active anhydride intermediate by using
alkyl chloroformate, adding a strong alkali solution of Fmoc-
lysine, reacting, adjusting the acid, extracting a product by using
ethyl acetate, combining organic phases, concentrating, purifying, and
drying to obtain the product. According to the method, amido bonds are formed in one pot, so that the purification process of the intermediate is reduced, the experimental steps are optimized, and the experimental cost is reduced.