We established an improved synthetic route to 4-chlorobenzo[b]thiophene, a key intermediate in brexpiprazole synthesis, via a practical decarboxylation process in three steps. Thermal analysis demonstrated that the coexistence of the decarboxylated product with DBU should be avoided and that removal of the product outside the reactor was vital. Our process yields the target compound by distillation under reduced pressure and is safe, highly batch efficient, cost-effective, and high yielding. Furthermore, manufacturing on a pilot scale was also accomplished through our approach.

中文翻译：

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安全高效的脱羧工艺：合成4-氯苯并[ b ]噻吩的实用方法

我们通过三个步骤进行实际的脱羧过程，建立了4-溴苯并[ b ]噻吩的关键合成中间体4-氯苯并[ b ]噻吩的改进合成路线。热分析表明，应避免脱羧产物与DBU的共存，并且除去反应器外的产物至关重要。我们的方法通过减压蒸馏来生产目标化合物，并且安全，批处理效率高，具有成本效益且产率高。此外，通过我们的方法还可以实现中试规模的制造。