Preparation method of 7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine

• Main Authors: XIE XIAOSHUAI, WANG PINGBAO, LIU DENGKE, LIU YING, NIU DUAN, MU SHUAI, ZHANG DASHUAI
• Format: Patent
• Language: Chinese; English
• Published: 03.04.2013
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

The invention relates to a preparation method of 7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine, which is an important intermediate for preparing arginine vasopressin V2 receptor antagonist Tolvaptan. The preparation method comprises the following steps: with methyl 2-amido-5-chlorobenzoate and ethyl 4-bromobutyrate as starting raw materials, reacting at a low temperature under the effect of an acid binding agent to generate secondary amine first, then carrying out Dieckman condensation reaction at a raised temperature to generate an intermediate mixture III, and finally carrying out hydrolysis to obtain the target compound 7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine. Compared with the existing method, the method provided by the invention has the advantages that the reaction steps are reduced, the two-step reaction is simplified to one-step reaction through temperature control, so the operation is simple, the processing is convenient, the product purity is high, and the yield is also greatly improv