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
Keywords:1,3-dicyclohexyl urea impurity, Grignard reaction, Racemization, Repaglinide, Resolution, Snar reaction, Telescopic process
AbstractThe 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.
How to Cite
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.
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