Tamsulosin Hydrochloride Synthesis Process Research

Benign prostatic hyperplasia (BPH) also known as benign prostatic hypertrophy (technically a misnomer), benign enlargement of the prostate (BEP), and adenofibromyomatous hyperplasia, refers to the increase in size of the prostate in elderly men. To be accurate, the process is one of hyperplasia rather than hypertrophy, but the nomenclature is often interchangeable, even amongst urologists.Adenomatous prostatic growth is believed to begin at approximately age 30 years. An estimated 50% of men have histologic evidence of BPH by age 50 years and 90% by age 80 years. In 40-50% of these patients, BPH becomes clinically significant.On a microscopic level, BPH can be seen in the vast majority of men as they age, in particular over the age of 70 years, around the world. However, rates of clinically significant, symptomatic BPH vary dramatically depending on lifestyle. Men that lead a western lifestyle have a much higher incidence of symptomatic BPH than men that lead a traditional or rural lifestyle. This is confirmed by research in China showing that men in rural areas have very low rates of clinical BPH, while men living in cities adopting a western lifestyle have a skyrocketing incidence of this condition, though it is still below rates seen in the West.Tamsulosin is the most common choice for BPH. It relax smooth muscle in the prostate,decreasing the blockage of urine flow.This paper, we aimed to research a synthetic path and its technics which was suitable for tamsulosin.1. In this paper, many literatures on Tamsulosin have been studied thoroughly, and the suitable synthetic path have been selected according to lab and industralization. In the synthetic path, Tamsulosin was synthesized using the main materials 4-Methoxyphenylacetone, and was synthesized by chlorosulfonatio, amination, hydrogenation,salify,hydrogenation,dissociation,received intermediated I. Then this intermediated I react with intermediated II which called amidogen ether,received the product tamsulosin. In this synthetic path, the main materials were cheap and facile, and its reaction conditions were moderate, and the disadvantages were avoided comparing with other synthetic paths of which main materials were not facile, and reaction conditions were stern, being short of selectivity.2. In this paper, the technics was researched thoroughly relating to the selection of reagent, reaction temperature, reaction time, compounding ratio and the methods of upper diaposal. The key side reactions were researched, and the methods of restraining side reactions and removing from by-products were brought up. In this paper the methods for disposing waste were offered. The technical condition was comparatively mature for industrialisation through technical optimization. Especially we use R-(+)-methylbenzylamine and 5-acetonyl-2-methoxybenzenesulfonamide in the presence of reducing agient to obtain high optical purity 1R,2R-2-methoxy-[2-(1-methylbenzylamino)-propyl]-benzensulfonamide(Ⅰ). This intermediate(Ⅰ) hydrogensis of intermediatedⅡto obtain tamsulosin.The process is capable of producing optically active R-(-)tamsulosin of high optical purity (> 99.0%) with hign reaction yield. The whole process involved chlorosulfonatio, amination, hydrogenation,salify,hydrogenation,dissociation,condensation etc. the total yield is 10.83%.3.The structure of target molecule was determined by UV,IR, MS,13C-NMR,1H-NMR TG-DSC,X-ray,NOESY. Also contrasted control article which from National institute for the control of pharmaceutical and biological products(B.A.100688-200401).4.The optical purity was determined by HPLC with CHIRAICEL OJ-H.To sum up, in this paper,many researches were carried out such as synthetic path design, technical research, quality research, lab validation, etc. The acquired technics was simple to operation, its raw materials were cheap and facile, and its yield and quality were steady, it was on terms to enviroment, and its material cost was cheap. The spectral analysis of finished product was carried out comparing with comparative product, which made sure that their structures were accordant. The finished product was proved out through assay. So the technics is suitable for industrialization. The tamsulosin technical research is advanced comparing with other open-eyed papers.