Study On The Preparation Process Of Amisulpride

Schizophrenia, which is a kind of persistent characteristics of chronic psychiatricdiseases, was rated for mental disease in one of the most serious diseases. Amisulpride,known as the representative of the second generation of new atypical antipsychotics, not onlypossesses all the feature of the first and second generation antipsychotics, but also has bettertolerability and safety, lower extrapyramidal side-effects incidence. It shows a good treatmentfor acute or chronic patients with positive and negative symptoms who need a long-termschizophenia maintenance treatment.The synthetic routes from literature were studied in detail. In view of safety and easyoperation in practice, a new synthetic route of amisulpride, a new atypical antipsychotic drug,was developed: using methyl 4-acetamido-2-methoxybenzoate as starting material, viasulfonation with sulfuric acid, hydrolysis, chlorination, reduction, reaction with bromoethaneand then hydrolysis to give 3-ethylsulfonyl-4-amino-6-methoxybenzoic acid, which wassubjected to condensation with 1-ethyl-2-(aminomethyl)pyrrolidine in the presence of ethylchloroformate and triethylamine. The effects of sulfonated agents, the orientation effect ofsubstituents, sulfonation temperature, ratio of raw materials, deacetylation reagents,deacetylation reaction time, chloride, chlorinated solvents, molar ratio of reactants inreduction reaction, ethylation conditions, solvents, and solvent refining were discussed, andthe appropriate conditions were determined for every process in the preparation. The preparedAmisulpride was confirmed by MS，1H NMR and elemental analysis. The overall yield wasabout 61 %. Meanwhile, the developed synthetic method possesses an advantage ofcommercially available starting materials, safe and easy operation, and thus a potential ofindustry practice.