The Synthesis Process Research Of Nicergoline

Nicergoline belongs to semi-synthetic ergot derivatives, and is widely used in the treatment of cognitive emotional and behavioral disorder alzheimer’s crowd of alzheimer’s disease in the current time. This disease is characterized by memory computing thinking language orientation force, the change of personality, social activity ability and self life ability decline. Because the elderly cerebral arteriosclerosis and degenerative diseases of the brain, each additional5years old, the percentage of alzheimers will rise2times, the prevalence of elderly population aged over60is1%, the prevalence of85people over the age of30%. In our country in1993, according to the survey for0.21%of the elderly over the age of60,65years of age or older population prevalence of0.35%, as China’s aging population is increasing, the number of drug market has huge potential for the treatment of alzheimer’s disease. In recent years of ergot Lin in vitro study of animal experiments and clinical trials for in-depth exploration, found its extensive pharmacological action mechanism and clinical application of indications, clinical use more widened, nicergoline its market prospect, of nicergoline demand. At present domestic no API manufacturers, agents with ergot forest raw materials mainly rely on import, greatly limits the nicergoline preparation production, the the synthetic technology study of nicergoline has good social benefit and economic benefit.This study combined with references and the supply of raw materials, adopt to ergot alcohol as the starting material for the synthesis, the photochemical reaction Methylation reaction and esterification reaction of three step synthesis, ergot Lin Carried out in accordance with the literature process experiment, in the aspect of color products and impurities is not in conformity with the quality requirements, in the process of the literature of operations affect enlarge pilot test, without considering the energy consumption and environmental protection at the same time, in view of the problems existing in the literature process design optimization of the technology was studied.First light chemical reaction generated after10alpha-methoxy-dihydro ergot alcohol (intermediate) color is optimized, optimizing reaction temperature change of ultraviolet lamp type Change the way light and try different active carbon decoloring methods such as conducting the test, finally USES the import C941activated carbon for decoloration method of the white solid; Second response to the methylation reaction temperature reaction solvent and methylation reagent conditions were optimized, such as reducing the hydroxyl ether by-products caused by impurities,0～5a product of the reaction temperature by ether with low content of impurities, the third step of refined to achieve quality standards. On the third step of esterification condensation agent types esterification reagent, the optimization of reaction temperature, determines the esterification reagent with smoke5-bromine chloride esterification reaction, after acetone refining, ergot Lin finished product The optimized process finished product all inspection according to quality standards, reach the qualified standard.During the study, after fully considering the reaction conditions of mass production, considering the product yield of quality operation and environmental protection, energy consumption is the synthetic technology of a zoom in a certain basis And optimize the structure of the obtained product, ergot Lin’s confirmed, confirmed the structure of the methods for the organic elemental analysis Ultraviolet spectrum infrared spectrum of nuclear magnetic resonance spectrum, X ray diffraction and thermal analysis, etc., by parsing conform to nicergoline’s structure characteristics.