An Improved Process for Repaglinide via an Efficient and One Pot Process of (1S)-3-methyl-1-(2-piperidin-1-ylphenyl)butan-1-amine – A Useful Intermediate

Authors

  • Naveenkumar Kolla
  • Chandrashekar R. Elati
  • Pravinchandra J. Vankawala
  • Srinivas Gangula
  • Eswaraiah Sajja
  • Yerremilli Anjaneyulu
  • Apurba Bhattacharya
  • Venkataraman Sundaram
  • Vijayavitthal T. Mathad

DOI:

https://doi.org/10.2533/chimia.2006.593

Keywords:

1,3-dicyclohexyl urea impurity, Grignard reaction, Racemization, Repaglinide, Resolution, Snar reaction, Telescopic process

Abstract

The development of a large-scale synthesis for (1S)-3-methyl-1-(2-piperidin-1-ylphenyl)butan-1-amine (S-(+)-1), a key intermediate of repaglinide (2), is described. The process conditions for S-(+)-1 involving nucleophilic substitution, Grignard reaction, reduction and resolution were optimized and telescoped. The racemization of the undesired enantiomer R-(?)-1 offers a distinctive advantage in terms of cost and overall yield over the existing process. This communication also describes the control of a DcU byproduct obtained during the condensation of S-(+)-1 with phenyl acetic acid derivative 3 in the synthesis of 2.

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Published

2006-09-01

Issue

Vol. 60 No. 9 (2006): Process Chemistry

Section

Scientific Articles

License

Copyright (c) 2006 Swiss Chemical Society

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

How to Cite

[1]
N. Kolla, C. R. Elati, P. J. Vankawala, S. Gangula, E. Sajja, Y. Anjaneyulu, A. Bhattacharya, V. Sundaram, V. T. Mathad, Chimia 2006, 60, 593, DOI: 10.2533/chimia.2006.593.