On the Fischer Indole Synthesis of 7-Ethyltryptophol-Mechanistic and Process Intensification Studies under Continuous Flow Conditions

7-Ethyltryptophol, a key intermediate in the synthesis of the anti-inflammatory agent etodolac, was produced by Fischer indole synthesis of 2-ethylphenylhydrazine and 2,3-dihydrofuran under continuous flow conditions. The reaction generates several undesired byproducts and therefore product yields could not be improved above 40-50%. The mechanism of this transformation was studied in detail and the structure of the byproducts carefully elucidated. Despite the only moderate product yield, the synthesis of 7-ethyltryptophol by this protocol remains interesting compared to alternative methods and starts from inexpensive reagents. The developed process is executed in an environmentally benign solvent (methanol) and, importantly, the majority of byproducts can be removed from the 7-ethyltryptophol product by a straightforward extraction process.