The Process Research And Development Of Chiral Amino-alcohol ((1S,2R)-2-(Benzylamino) Cyclohexyl) Methanol

As the new scientific payoffs spring up,the transformation of scientific achivements into large-scale operation has gained more attention,especially in the field of organic synthesis.As an important organic synthesis,asymmetric synthesis has been widely used in fine chemical industry.While in medical area,it is performing a revolutionary function by bringing human the chiral medicine,as well as getting rid of the side-effects.So that curative effect will be improved.Because of its high efficiency in obtaining highly optically active compounds,asymmetric synthesis,which is one of the most important way to get chiral compounds,are attracting increasing attention.Chiral amino-alcohol,as an important member of chiral compounds,were widely used in clinical studies as drugs or components of drugs.In this article,the synthetic process of??1S,2R?-2-?benzylamino?cyclohexyl?methanol,which is one of the chiral alkamine,will be studied,and the pilot scale-up of this compound will be studied.The chemical reactions used in the synthesis of this compound will be discussed in depth.The article focus on thouse reactions,condensation reaction,asymmetric synthesis,reductive amination,hydrogenolysis of benzyl and reduction reaction of ester.In particular,the asymmetric synthesis step get the stereoselectivity in up to 9:1.The process of synthesizing high optical purity compounds by using R-phenethylamine as chiral inducing reagent was emphatically discussed.The stereoselectivity was achieved by 1:9.At the same time,the high efficient reductive reagents used during the process,such as:NaBH₄,NaB?OAc?₃H,LiAlH₄ and Red-Al have been studied correspondingly.Base on this compound,this article discussed how to transfer the laboratory process to pilot scale.Starting from the lab-scale studies to find out the process issues.Some experiments are designed to solove those issues and the experimental data is collected,then the issues are solved.On the purpose of ensuring the safety of the industrial system,partial of the process operation is optimized and the hazard materials are replaced,especially intrinsically safe replacement the NaH and LiAlH₄which are generally considered as high-risk materials.Process Hazard Analysis and Process Thermal Risk Test Report tell us the potential safety issues,the issues are optimized in the lab before scale-up.The highest efficiency is the requirement of industrialization and some optimization are implemented.Adjust the process to minimize the equipment occupancy and reduce the unit operating time to get the target.