Copyright (c) 2026 srinivas garaga, harikiran M.N.V.D, vekariya N.A, raghubabu korupolu, suribabu madasu, paul douglas sanasi
This work is licensed under a Creative Commons Attribution 4.0 International License.
An Efficient Racemization Process of Tolterodine using Potassium tert-Butoxide in DMSO
Corresponding Author(s) : Srinivas Garaga
Asian Journal of Chemistry,
Vol. 38 No. 9 (2026): Vol 38 Issue 9 Year 2026
Abstract
A novel racemization process was developed for the conversion of (S)-tolterodine, obtained as a byproduct during the resolution of racemic tolterodine, into racemic (R,S)-tolterodine. The process involves protection of the phenolic hydroxyl group with benzyl chloride, followed by racemization using potassium tert-butoxide in DMSO at 60-65 ºC. Subsequent debenzylation with Raney nickel afforded racemic tolterodine, which was resolved with L-(+)-tartaric acid to obtain tolterodine tartrate. The racemization of the undesired (S)-enantiomer enables its recycling into the resolution process, thereby reducing material loss and providing a practical approach for improving the yield of the desired (R)-tolterodine.
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- U. Jonas, K. Hofner, H. Madersbacher and T.H. Holmdahl, World J. Urol., 15, 144 (1997); https://doi.org/10.1007/BF02201987
- L. Nilvebrant, K.-E. Andersson, P.-G. Gillberg, M. Stahl and B. Sparf, Eur. J. Pharmacol., 327, 195 (1997); https://doi.org/10.1016/S0014-2999(97)89661-6
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- C. Botteghi, T. Corrias, M. Marchetti, S. Paganelli and O. Piccolo, Org. Process Res. Dev., 6, 379 (2002); https://doi.org/10.1021/op020014k
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References
U. Jonas, K. Hofner, H. Madersbacher and T.H. Holmdahl, World J. Urol., 15, 144 (1997); https://doi.org/10.1007/BF02201987
L. Nilvebrant, K.-E. Andersson, P.-G. Gillberg, M. Stahl and B. Sparf, Eur. J. Pharmacol., 327, 195 (1997); https://doi.org/10.1016/S0014-2999(97)89661-6
E. Gianolli, E. Giannini, L. Bigini, O. Piccolo, P. Holmberg and T. Lundholm, Process for the Preparation of N,N-Diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenylpropylamine and its Salts, PCT Int. Appl., WO 2012098044 A1 (2012).
K. Kobayashi, T. Nishikata, Y. Yamamoto and N. Miyaura, Bull. Chem. Soc. Jpn., 81, 1019 (2008); https://doi.org/10.1246/bcsj.81.1019
G. Wang, J. Zhang, X. He and Y. Wang, Process for Preparation of Tolterodine and Tartrate, Faming Zhuanli Shenqing, CN 101445462 A (2009).
A. Kompella, R. Srinivasa Thungathuthy, K. Adibhtla, R. Bhujanga, C. Venkaiah and Nannapaneni, Process for the Preparation of an Intermediate useful in the Synthesis of Tolterodine, Indian Patent Application, IN 2003CH01028 A (2005).
G. Razzetti, S. Mantegazza, R. Rossi and P. Allegrini, A Process for the Preparation of Tolterodine, Eur. Pat. Appl., EP 1693361 A1 (2006).
A. N. Jonsson, B.A. Spárt, L. Mikiver, P. Moses, L. Saltsjö-Boo and G. Nilvebrant, 3,3-Diphenylpropylamines and Pharmaceutical Composi-tions thereof, U.S. Patent 5,382,600 (1995).
K. Srinivas, N. Srinivasan, K.S. Reddy, M. Ramakrishna, C.R. Reddy, M. Arunagiri, R.L. Kumari, S. Venkataraman and V.T. Mathad, Org. Proc. Res. Dev., 9, 314 (2005); https://doi.org/10.1021/op050024w
C. Botteghi, T. Corrias, M. Marchetti, S. Paganelli and O. Piccolo, Org. Process Res. Dev., 6, 379 (2002); https://doi.org/10.1021/op020014k
F. Ulgheri, M. Marchetti and O. Piccolo, J. Org. Chem., 72, 6056 (2007); https://doi.org/10.1021/jo0705667
K.S. Rao, K.N. Rao, P. Muralikrishna and A. Jayashree, Asian J, Chem., 26, 2813 (2014); https://doi.org/10.14233/ajchem.2014.15708
G. Srinivas, A.V.R. Reddy, K.J. Prabahar, K. Prasada Rao, P.D. Sanasi and R. Korupolu, Sustain. Chem. Process., 2, 2 (2014); https://doi.org/10.1186/2043-7129-2-2
