Reissert Indole Synthesis Using Continuous-Flow Hydrogenation

A series of substituted indole-2-carboxylic acid ethyl esters and aza-indole analogs have been prepared using continuous-flow hydrogenation. The identification of some key parameters using a design of experiments (DoE)-based approach allowed efficient optimization of each synthesis. The scale-up study for the multigram preparation of one model indole substrate showed the importance of working at steady state with the H-Cube apparatus. A new useful method for the easy preparation of substituted indoles in various quantities is presented.