91342-74-4Relevant articles and documents
Real-Time Monitoring of Solid-Liquid Slurries: Optimized Synthesis of Tetrabenazine
Sato, Yusuke,Liu, Junliang,Kukor, Andrew J.,Culhane, Jeffrey C.,Tucker, John L.,Kucera, David J.,Cochran, Brian M.,Hein, Jason E.
, p. 14069 - 14078 (2021/07/26)
Solid-liquid slurries are vital and increasingly prevalent in the pharmaceutical and chemical industries. Despite the importance of these heterogeneous systems, process control and optimization are fundamentally hindered by a lack of compatible real-time analytical techniques. We present herein an online HPLC monitoring platform enabling access to real-time compositional information on slurries. We demonstrate the system by investigating the heterogeneous synthesis reaction of tetrabenazine. Furthermore, we integrated our online HPLC platform with the orthogonal monitoring techniques of a pH probe and a microscopic imaging probe to provide additional mechanistic insight. These combined insights enable the optimization of tetrabenazine synthesis in terms of reaction time, byproduct formation, and diastereomeric purity of the final product.
The synthesis of precursor of FP- (+) DTBZ
Wu, Caijiao,Li, Hui,Sun, Feiyang,Bao, Changshun,Bao, Xuefei,Chen, Guoliang
supporting information, p. 3218 - 3225 (2019/09/13)
A synthetic route to the precursor of FP- (+) DTBZ was disclosed, in which 3-hydroxy-4-methoxybenzaldehyde was employed as a starting material. In the method, the benzyl-protecting protocol and the in-situ Diels-Alder reaction made the procedure more practical because of the mild conditions for selectively deprotection and the accelerated reaction process.
Synthetic method for tetrabenazine and intermediate of tetrabenazine
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Paragraph 0018, (2018/03/26)
The invention discloses a simple and effective method for synthesizing tetrabenazine (cis-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-3-isobutyl-2H-benzo[a]quinolizin-2-one) and an intermediate of the tetrabenazine. The method comprises the following steps: firstly, paraformaldehyde, dimethylamine hydrochloride and 5-methyl-2-hexanone are taken as raw materials to synthesize a key intermediate 3-dimethylaminomethyl-5-methyl-2-hexanone; secondly, a crude product is effectively optimized by using simple chemical purification operation to obtain a key intermediate with higher purity; and finally, water is taken as a solvent, under the action of a catalyst, the purified key intermediate and 6,7-dimethoxy-3,4-dihydroisoquinoline hydrochloride are subjected to condensation to obtain a tetrabenazine crude product, and recrystallization is performed to obtain the tetrabenazine product, wherein the HPLC purity is greater than 99.5%. According to the method provided by the invention, the key intermediate with higher purity can be obtained by the simple chemical raw materials through synthesis and purification, and therefore the tetrabenazine product with good purity is further obtained; and the raw materials used in the method are easy to obtain, the operation is simple, special equipment is not needed, the yield is higher, and the obtained tetrabenazine has higher purity.
