摘要本设计是对年产25吨阿奇沙坦缩合和环合工段进行工艺设计，编制设计说明书。阿奇沙坦的生产是以原碳酸四乙酯等为原料，经环合、加成、缩合、环合、水解等五步反应得阿奇沙坦粗品，再经精制得阿奇沙坦成品。缩合工序是以加成工序的产物AZ-7与三乙胺、氯甲酸乙酯、二氯甲烷等作为原料，然后经过反应得中间体AZ-8，最后与乙醇反应得AZ-9。

设计内容主要是根据已有的缩合工序和环合工序工艺路线对阿奇沙坦进行物料衡算，在物料衡算的计算结果的基础上再进行能量衡算，并且对缩合和环合工序中涉及到的主要设备进行选型，公用工程主管的管径计算，车间布置，以及查阅相关资料撰写GMP专篇、行政法规执行措施。最后，对本次设计过程中的亮点，存在的问题作出总结。并且绘制了工艺管道及仪表流程图（PID）、车间设备平面布置图、车间平面布置图等设计图纸。79611

毕业论文关键词: 阿奇沙坦；工艺设计；物料衡算；能量衡算；设备选型

Process design of an annual output of 25 tons of azisartan in candesartan condensation and cyclization process

Abstract   The design is an annual output of 25 tons of azilsartan in condensation and cyclization workshop section of the process design and preparing the design specifications。The production of azilsartan is based on tetraethyl orthoscarbonate as raw material, by the cyclization, addition, condensation, cyclization, hydrolysis of five-step reactions, the azilsartan crude products is got, and then purify it to get finished product of azilsartan。The condensation process takes the product AZ-7 of the addition process and triethylamine, ethyl chloroformate, dichloromethane as raw materials, and then get intermediate AZ-8 through the reaction , and finally reacted with ethanol to AZ-9。

The design content is mainly based on the existing condensation process and the ring process route to the complete the material balance of azilsartan。According to the calculation of the results of material balance and then to complete the energy balance, and the selection of the main equipment involved in the condensation and cyclization workshop section,calculation of pipe diameter of utilities main piping,plant layout,as well as access to relevant information to write GMP articles,administrative regulations enforcement measures,Finally,I summarize the highlights of the design process and  the existing problems。And draw the process pipeline and instrument flow chart (PID), workshop equipment layout plan, the workshop layout plan and other design drawings。

Keywords:  Azilsartan；process design；material balance；energy balance；equippment selection

目  录

摘要 2

Abstract 2

1  绪论 7

1。1 新一代治疗高血压药——阿奇沙坦 7

1。2 国内阿奇沙坦市场及研究发展情况 8

1。2。1 国内市场情况 8

1。2。2 国内临床研究情况 8

1。3 国际阿奇沙坦市场及研究发展现状 9

1。3。1 国际市场现状 9

1。3。2 国际研究发展情况 9

1。4 经典合成方法存在的问题及优化改进 11

1。4。1 氯甲酸酯分步环化法优化 12

1。4。2 羰基环化法合成阿奇沙坦的优化 12