Preparation method of litamilast intermediate

• Main Authors: DENG JUN, YUAN SHUAI, ZHANG ZHENFENG, LUO TONGYOU, TAN ZHENYOU, NING ZUOCHAO
• Format: Patent
• Language: Chinese; English
• Published: 14.03.2023
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

The invention relates to a preparation method of a litamilast intermediate compound 1, which comprises the following steps: adopting a specific copper ligand compound, a reaction organic solvent and sodium hydroxide to obtain a compound 4, acidifying the compound 4 in the presence of the specific organic solvent, adding a chelating agent, alkalifying to obtain a compound 5, acidifying, and recovering a catalyst compound 6 to obtain the litamilast intermediate compound 1. And reacting the compound 5 with Boc anhydride to obtain a target compound 1. The method is high in reaction stereoselectivity, low in isomer and disubstituted impurity content, free of purification and capable of being directly used for subsequent synthesis reaction of litamilast. 本发明涉及一种立他司特中间体化合物1的制备方法，采用特定的铜配体化合物，反应有机溶剂和氢氧化钠，得到化合物4，化合物4在特定有机溶剂下，酸化，加入螯合剂后碱化，得到化合物5，酸化后回收催化剂化合物6，化合物5与Boc酸酐反应得到目标化合物1。本方法反应立体选择性高，异构体及二取代杂质含量低，无需纯化，可直接用于后续立他司特的合成反应。