The invention relates to a preparation method of 2-(2-fluoro-4-
biphenyl) propionic acid. The preparation method comprises the following steps: by taking 2, 4-difluoronitrobenzene as an initial
raw material, carrying out
substitution reaction on the 2, 4-difluoronitrobenzene and diethyl 2-methylmalonate to obtain diethyl 2-(3-fluoro-4-nitrophenyl)-2-methylmalonate; reducing the 2-(3-fluoro-4-nitrophenyl)-2-diethyl methylmalonate, so as to obtain 2-(4-amino-3-fluorophenyl)-2-diethyl methylmalonate; carrying out reduction on the 2-(3-fluoro-4-nitrophenyl)-2-diethyl methylmalonate to obtain 2-(4-amino-3-fluorophenyl)-2-diethyl methylmalonate; the preparation method comprises the following steps: diazotizing 2-(4-amino-3-fluorophenyl)-2-diethyl methylmalonate to obtain diazonium salt, and reacting the diazonium salt with tetrahydroxy
diborane or
boric acid ester to obtain 2-(3-fluoro-4-
boric acid phenyl)-2-diethyl methylmalonate or 2-(3-fluoro-4-
boric acid pinacol ester phenyl)-2-diethyl methylmalonate; the preparation method comprises the following steps: carrying out Suzuki-Miyaura
coupling on 2-(3-fluoro-4-boric acid phenyl)-2-diethyl methylmalonate or 2-(3-fluoro-4-boric acid
pinacol ester phenyl)-2-diethyl methylmalonate and halogenated
benzene to obtain 2-(2-fluoro-4-
biphenyl)-2-diethyl methylmalonate; carrying out Suzuki-Miyaura
coupling on the 2-(3-fluoro-4-boric acid
pinacol ester phenyl)-2-diethyl methylmalonate or 2-(3-fluoro-4-boric acid pinacol ester phenyl)-2-diethyl methylmalonate and halogenated
benzene to obtain 2-(2-fluoro-4-
biphenyl)-2-diethyl methylmalonate; and 2-(2-fluoro-4-biphenyl)-2-diethyl methylmalonate is subjected to
hydrolysis and
decarboxylation, such that the target product 2-(2-fluoro-4-biphenyl) propionic acid is obtained. In the process
route, starting materials are cheap and easy to obtain, operation is simple, aftertreatment is convenient, harsh
reaction conditions such as high temperature and
high pressure are avoided, and industrial production is facilitated.