Studies On The Asymmetric Synthesis Of(R)-(+)-3-chloro-1-phenyl-1-propanol Via An Efficient Chiral Catalyst

(R)-(+)-3-chloro-1-phenyl-1-propanol is the important chiral intermediate of the paroxetine antidepressants and some inhibitor drugs.Preparation of it was the key unit,and has been studies widely at home and abroad.With the increasing spread of depression,the synthesis of high optical purity of(R)-(+)-3-chloro-1-phenyl-1-propanol has important medicinal values and broad market prospects.In this work,chiral spiral borate ester A,which has good enantioselectivity on aromatic alkyl ketones,was applied as catalyst for the asymmetric reduction of 3-Chloropropiophenone in synthesis of(R)-(+)-3-chloro-1-phenyl-1-propanol.Bisides,The process of chiral spiral borate ester A was improved:the reaction can proceed without inert gas;green solven L was instead of toxic toluene in the reaction environment.The result shows that the catalytic performance and stability has improved on this process.In the research of asymmetric synthetic reaction,the analytical mehtod by chiral GC was set up to chase the experiment.Main influencing factors was investigated with single-factor and orthogonal experiments.The results showed that,when the process was taken on 3-Chloropropiophenone as the basis with 0.09 equivalent of catalyst and 0.6 equivalent of borane at 5? for 4 h,the experiment obtained conversion rate of 99.33%and optical purity of 96.37%e.e.values.The product(R)-(+)-3-chloro-1-phenyl-1-propanol,a few unreacted 3-Chloropropiophenone and other impurities were separated by silica gel column chromatography.The volume ratio of the eluent ethyl acetate and petroleum ether,was primarily investigated.The experiment results indicated that there was the best separation results with the volume ratio of 1:8.The purified product(R)-(+)-3-chloro-1-phenyl-1-propanol was determined by IR,1H NRM,melting piont and optical rotation.The structure and configuration were accordant to the properties of the compound.