The invention relates to the technical field of synthesis of
fluorine-containing heterocyclic compounds, and discloses a preparation method of 3-phthalimido-2, 2-difluoropropionic acid, which comprises the following steps: reacting
phthalimide potassium salt, 3-halo-2, 2-difluoropropionate,
polyamine organic alkali serving as a synergistic activator and N, N-
dimethylformamide serving as a structural stable factor in a
solvent to prepare 3-phthalimido-2, 2-difluoropropionic acid, thereby obtaining the 3-phthalimido-2, 2-difluoropropionic acid. The method comprises the following steps: putting N, N '-
dimethylurea into an aprotic polar
solvent containing cyclic organic
carbonate to construct a heterogeneous
reaction system; a
reaction system is controlled to be subjected to a
nucleophilic substitution reaction, an intermolecular
hydrogen bond association body is formed by using a structure stable factor and two symmetrical carbonyl
oxygen atoms of a
phthalimide anion, a nucleophilic
attack path of the anion to a self heterocyclic skeleton is blocked, and a target product is obtained through acidic
hydrolysis after an intermediate is generated. Through an intermolecular precise charge shielding mechanism, the contradiction between activity and stability in the
nucleophilic substitution process is solved, the ring-opening
side reaction is inhibited, and the product purity is improved.