= Bornyl Acetate Synthesis Process Optimization Design

Danshensu borneol ester (DBZ) is a novel synthetic compound derived from the traditional Chinese medicine (TCM) theory, which is effective on cardiovascular and cerebrovascular diseases. Scale-up is an important prerequisite for drug development towards drug production. It not only provide sufficient drug for the drug’s preclinical pharmacology and toxicology studies and clinical trials, but also pave the way for the industrial production of drug to reduce the risk of drug production. During the study of the DBZ synthetic route, we explored a novel line which has high yield and low pollution and is easily operated through querying references and a series of experiments. The new line in our research can provide enough compound for the development of DBZ.The new synthetic route of DBZ remove the synthesis of (Z)-2-acetamido-3-(3,4-diacetoxyphenyl) acrylic acid and the3-(3,4-dihydroxyphenyl)-2-oxopropanoic acid is synthesized in a signal reaction. The effects of the solution volume of hydrochloric acid and acetone and reaction time on yield of this reaction were investigated by the methods of the gradient experiments of single factor and multilevel orthogonal design. In the process of etherification, the catalyst is anhydrous sulfanilic acid which is commercialized, to replace the solid super-acid S2O82-/ZrO2which is operated complexly. The effects of dehydrating agents on yield of this reaction were investigated. In the process of reduction, the catalyst is Pd/C catalyst to replace the Zn(Hg) catalyst which is harmful to environment.The reaction is tracking by thin layer chromatography (TLC), and the product is identified and the purity is determinated by the use of infrared spectroscopy(IR), high performance liquid chromatography(HPLC) and nuclear magnetic resonace(NMR).During the scale-up of DBZ, we select the different reactor of5L、20L、500L and explored the influence on the reaction of the reaction time and temperature with the increase of the reaction volume. The purity of DBZ arise from70%in the original route to95%in the new route by continuous experiments and process optimization, and there is much convenient in the isolation and purification of DBZ.