Asymmetric synthesis method of optically pure (R)/(S)-hydroxychloroquine side chain

• Main Authors: ZHENG YONGPENG, ZHAO JINHUI, DING XIAOBING, LIU CHUANGJI
• Format: Patent
• Language: Chinese; English
• Published: 18.02.2022
• Subjects: APPARATUS THEREFOR; CHEMISTRY; GENERAL METHODS OF ORGANIC CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

The invention provides a method for synthesizing optically pure (R)/(S)-hydroxychloroquine, which comprises the following steps: resolving (+/-)-2-[(4-aminoamyl)ethylamino]ethanol by using a resolving reagent, recrystallizing and purifying the compound to obtain optically pure (R)/(S)-2-[(4-aminoamyl)ethylamino]ethanol; and reacting the obtained single-configuration hydroxychloroquine side chain with 4,7-dichloroquinoline to obtain the hydroxychloroquine sulfate of single configuration. The method has the advantages of simple route, easily available raw materials, high yield, good stereoselectivity (ee% is greater than 99%), simple operation, greenness and environmental protection, and is suitable for large-scale production. 本发明提供了一种光学纯(R)/(S)-羟氯喹合成方法，利用拆分试剂对(±)-2-[(4-氨基戊基)乙胺基]乙醇进行拆分，并进行重结晶纯化，纯化后得到光学纯的(R)/(S)-2-[(4-氨基戊基)乙胺基]乙醇，将得到的单一构型羟氯喹侧链与4,7-二氯喹啉反应直接得到单一构型的羟氯喹硫酸盐。该方法路线简单，原料易得，产率高，立体选择性好(ee％＞99％)，操作简单绿色环保，适用于规模化放大生产。