Manufacturing synthesis of 5-hydroxy-2-methyl-1H-
Received: 26 August 2010 / Accepted: 1 November 2010 / Published online: 18 November 2010
Ó Springer Science+Business Media B.V. 2010
Abstract The manufacturing synthesis of 5-hydroxy-2-methyl-1H-indole is
described and two synthetic methods were used and the results discussed. Two small
and three large runs with Nenitzescu’s method were analyzed and results reported
with different reaction conditions. Manufacturing issues encountered were dis-
cussed. Production scale of more than 60 kg of the 5-hydroxy-2-methyl-1H-indole-
3-carboxylic acid ethyl ester and over 20 kg of the 5-hydroxy-2-methyl-1H-indole
were achieved. Based on these results, larger scale manufacturing of this product or
similar products based on the optimized conditions is feasible.
Keywords 5-Hydroxy-2-methyl-1H-indole Á Nenitzescu Á Benzoquinone Á
Indole structure is one of the most important members of heterocyclic compounds
and is a ‘‘privileged scaffold’’ for many natural and pharmaceutical products .
For example,well known pharmaceutical/natural products Tryptophan, Indometacin,
Medmain, Serotonin, Melatonin, Oxypertine, Vinblastin, etc. contain indole
moieties. Many alkaloids from plants and from marine sources have indole
Numerous products of pharmaceutical interest contain the structure of 2-methyl-
5-hydroxy-1H-indole. A series of ethyl 2-alkyl-6-bromo-5-hydroxy-1H-indole-3-
carboxylate derivatives were found to be effective against inﬂuenza virus .
Similar structures were also demonstrated to be active against hepatitis B virus .
Y.-S. Huang (&) Á W.-Q. Zhang Á X. Zhang Á J.-Z. Wang
Guangdong Medical College School of Pharmacy, 1 Xincheng Ave,
Songshan Lake Technology Park, Dongguan 523808, China
Res Chem Intermed (2010) 36:975–983