Study On Synthetic Process Of(R)-1,1'-Binaphthyl-2,2'-Dicarboxylic Acid And Dapoxetine

Chirality is one of the essential characteristics of the nature, which is the main difference between living matter and nonliving matter. On the one hand, some of the chiral molecules, can be used as chiral catalysts and chiral ligands. These chiral catalysts and chiral ligands demonstrate high chemical selectivity and enantioselectivity in asymmetric catalytic reactions, which result in high productivity and economic efficiency in asymmetric catalytic reactions. On the other hand, taking the drug which has two enantiomers into account, the two different enantiomers are absorbed, activated and degraded through different ways, which means that the chirality is directly related to clinical effects, pharmacological effects, side effects, efficacy time and the efficacy of drugs.1,1'-Binaphthyl-2,2'-dicarboxylic acid with optical purity is an important catalyst, ligand and synthetic intermediate in asymmetric reactions. So far, reported synthesis methods of1,1'-Binaphthyl-2,2'-dicarboxylic acid with optical purity cost too much, not favorable for industrial production, to a great degree, hindering the research and application of such catalysts and related catalytic asymmetric reactions.In this thesis, the starting material is (R)-Binaphthol, which finally affords (R)-1,1'-Binaphthyl-2,2'-Dicarboxylic Acid via Trifluoromethyl Sulfonation, Methylation, Bromination, Hydrolysis and Oxidation, successively. On the basis of the literature and patents, we invent the novel synthetic route, which is simple and applicable. In addition, we synthesized the precursor substrates for Beckmann rearrangement reaction, which are3-substituted cyclobutanone.In this thesis, we explored the synthesis of Dapoxetine as well. Dapoxetine is a drug used to treat premature ejaculation, which is most widely used, significantly effective and being developed faster in clinic so far. Dapoxetine was used to treat depression, which is one of SSRIs. In recent years, it is used to treat premature ejaculation, and it shows good clinical effects. The starting material are Benzaldehyde and malonic acid, which finally afford rac-N,N-dimethyl-3-(naphthalen-1-yloxy)-1-phenylpropan-1-amine via Knoevenagel reaction, Reduction by NaBH4-I2, Eschweiler-Clark reaction, Williamson reaction, successively. Furthermore, we tried to resolve rac-N,N-dimethyl-3-(naphthalen-1-y loxy)-1-phenylpropan-1-amine by L-tartaric, failed to get the crystal, so the further exploration of the resolution condition is necessary. This synthetic route makes use of raw materials which are cheap and easy to get effectively, each reaction is simple and applicable, which is favorable to reducing pollution and costing down, resulting in significant good social effects and economic benefits. After optimizing the synthesis process of Dapoxetine, this synthetic route is expected to realize industrialization.