Abstract

An efficient large-scale preparation of 2-chlorotetrahydroquinoline with cyclohexanone and benzylamine as starting materials was developed and well optimized, in which benzyl-protected enamide was successfully cyclized and benzyl group was directly removed under Vilsmeier conditions. Azeotropic distillation provided 264 g of 2-chlorotetrahydroquinoline (79%) on a 2 mol scale of reaction without intermediate isolation. The downstream product 2-chlorotetrahydroquinolin-8-one was acquired through Boekelheide rearrangement, hydrolysis of acetate via NaBH₄ reduction, and Anelli oxidation. With the developed procedure, the intermediates were not necessary to be isolated and 2-chlorotetrahydroquinolin-8-one was conveniently obtained with solvent slurry in 65% overall isolated yield in a four-step sequence.

中文翻译：

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大规模合成2-氯四氢喹啉和2-氯四氢喹啉-8-one

摘要

开发并有效优化了以环己酮和苄胺为原料的2-氯四氢喹啉的高效大规模制备方法，该方法成功地使苄基保护的酰胺环化，并在维尔斯迈尔条件下直接去除了苄基。共沸蒸馏以2mol的反应规模提供264g的2-氯四氢喹啉（79％），而无需中间分离。下游产物2-氯四氢喹啉-8-一通过Boekelheide重排，NaBH ₄还原将乙酸酯水解和Anelli氧化而获得。通过开发的方法，不必分离中间体，可以方便地用溶剂淤浆以四步顺序以65％的总分离产率获得2-氯四氢喹啉-8-一。