Open AccessAn 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
Author(s) -
Naveenkumar Kolla,
Chandrashekar R. Elati,
Pravinchandra J. Vankawala,
Srinivas Gangula,
S. Eswaraiah,
Yerremilli Anjaneyulu,
Apurba Bhattacharya,
Venkataraman Sundaram,
Vijayavitthal T. Mathad
Publication year - 2006
Publication title -
chimia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.387
H-Index - 55
eISSN - 2673-2424
pISSN - 0009-4293
DOI - 10.2533/chimia.2006.593
Subject(s) - racemization , yield (engineering) , chemistry , amine gas treating , acetic acid , condensation , organic chemistry , derivative (finance) , enantiomer , nucleophilic substitution , combinatorial chemistry , materials science , physics , economics , financial economics , metallurgy , thermodynamics
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.