Telescoped Hybrid Batch–Flow Synthesis of 2-Butylbenzofuran

The present work describes the development of an improved synthesis of the pharmaceutically relevant building block 2-butylbenzofuran (BBF). The telescoped hybrid batch–flow process is composed of three steps and affords the final product in high yield and purity. The key cyclization step is performed in continuous mode with integrated workup: this approach is more efficient compared to the standard batch conditions. The high quality of the product makes crude BBF suitable to be used in the downstream process of production of amiodarone without purification. The optimization was realized using the Design of Experiments approach and afforded a sustainable process suitable for industrial application.