Synthesis method of tolterodine and enantiomers thereof

• Main Authors: ZHU WANJIANG, YAO JIAN, DOU XIAOWEI, XING JUNHAO
• Format: Patent
• Language: Chinese; English
• Published: 13.09.2019
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; METALLURGY; ORGANIC CHEMISTRY

Belonging to the field of chemical synthesis, the invention discloses a synthesis method of tolterodine and enantiomers thereof. The method includes: taking cinnamaldehyde as the raw material for asymmetric arylation reaction with (2-hydroxy-5-methylphenyl)boric acid under the action of a rhodium catalyst to obtain a hemiacetal intermediate, and subjecting the hemiacetal intermediate directly to reductive amination reaction without purification, thus obtaining high optically pure tolterodine. 2-hydroxyl-5-methyl cinnamaldehyde and phenylboronic acid are taken as the starting raw materials, andthe same synthesis method and operation steps are employed to prepare high optically pure tolterodine enantiomers. The method reported by the invention has the characteristics of short route, high total yield, good stereoselectivity and the like, and the ee values of the two synthesized configuration products are both greater than 99%. 本发明公开了一种托特罗定及其对映体的合成方法，属于化学合成领域。本发明以肉桂醛为原料，在铑催化剂的作用下，与(2-羟基-5-甲基苯基)硼酸发生不对称芳基化反应，得到的半缩醛