Preparation method of (R,S)-2-[[5-(9-fluorenemethoxycarbonylamino)dibenzo[A,D]cycloheptane-2-yl]oxyl]acetic acid

The invention relates to a preparation method of Ramage linker and mainly solves problems of long processes, complex post-treatment, much waste water, waste gas and solid waste, and high cost in a conventional synthetic method. The preparation method includes following steps: (A) carrying out a reaction to 2-carboxybenzaldehyde and m-methoxyphenylacetic acid to obtain an intermediate 2-(3-methoxylstyryl)benzoic acid, dissolving the intermediate with a solvent, performing hydrogenation reduction, and performing post-treatment crystallization to obtain a compound R-1; (B) carrying out a reaction to the R-1 with SOCl2 or POCl3 to obtain 2-methoxyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-one, performing negative-pressure evaporation to remove the SOCl2 or the POCl3, dissolving the 2-methoxyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-one in benzene, methylbenzene or 1,2-dichloroethane, performing a catalytic reaction with anhydrous AlCl3 and performing post-treatment crystallization to obtain a compound R-2; (C) carrying out a reaction to the R-2 with benzyl bromoacetate in DMF or an acetone/K2CO3 solution to obtain a compound R-3; (D) performing hydrogenation reduction to the R-3 to obtain a compound R-4; and (E) adding a catalyic amount of PTS to the R-4 in DMF and carrying out a reaction to the R-4 with Fmoc-NH2 to obtain the Ramage linker, which is an effective C-terminal linker in solid-phase synthesis.