posted on 2013-02-15, 00:00authored byBernhard Gutmann, Michael Gottsponer, Petteri Elsner, David Cantillo, Dominique M. Roberge, C. Oliver Kappe
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.