A New and Improved Process for N-(4-Chloro-3-cyano-7-ethoxyquinolin-6-yl)acetamide

作者:Mao Yongjun; Liu Zheng; Yang Xiaojun; Xia Xiangfei; Zhang Rongxia; Li Jianfeng; Jiang Xiangrui; Xie Kai; Zheng Jin; Zhang Hui; Suo Jin; Shen Jingshan*
来源:Organic Process Research & Development, 2012, 16(12): 1970-1973.
DOI:10.1021/op300260m

摘要

A new and improved synthetic route to N-(4-chloro-3-cyano-7-ethoxyquinolin-6-yl)acetamide (1) is described on a kilogram scale. The key step is the basic cyclization of o-[(2-cyanovinyl)amino]benzoate (14) in (BuONa)-Bu-t/(BuOH)-Bu-t system to give the 3-cyano-4-hydroxyquinoline (7). The final product 1 is obtained with 49% overall yield (seven steps) and 98.9% purity (HPLC), which makes it a cost-effective and commercially friendly process for scale-up operations.

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