A Simple and Efficient Asymmetric Synthesis of Anxiolytic Drug Enciprazine

Abstract

A straightforward and efficient asymmetric synthesis of (S)-1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-(3,4,5-trimethoxyphen­oxy)propan-2-ol is described. The key intermediate, (S)-2-[(3,4,5-trimethoxyphenoxy)methyl]oxirane, was obtained by a hydrolytic kinetic resolution method using the catalyst (R,R)-salen-cobalt(III) complex.

trimethoxyphenol - resolution - chiral epoxide - meth­oxy­benzenamine

References

1a Frishman WH. New Engl. J. Med.  1981,  305:  500 

1b Lohmann D. Lehmann D. Morgenstern E. Faust G. Pharmazie  1990,  45:  401 

1c Nickel B. Szelenyi I. Neuropharmacology  1989,  28:  799 

1d Engel I. Kleemann A. Jakovlev V. Drugs Future  1981,  6:  278 

1e Engel J. Fleischhauer I. Jakovlev V. Kleemann A. Kutscher B. Nickel B. Rauer H. Werner U. Szelenyi I. J. Med. Chem.  1990,  33:  2976 

2a Soboleva SG. Galatin AF. Karaseva TL. Golturenko AV. Andronati SA. Pharm. Chem. J.  2005,  39:  236 

2b Ferretti RB. Gallinella F. Torre L. Zanitti L. J. Liq. Chromatogr. Relat. Technol.  1999,  22:  1877 

3a Bose DS. Narsaiah AV. Bioorg. Med. Chem.  2005,  13:  627 

3b Narsaiah AV. Synth. Commun.  2006,  36:  1897 

4a Tokunaga M. Larrow JF. Kakiuchi F. Jacobsen EN. Science  1997,  277:  936 

4b Annis DA. Jacobsen EN. J. Am. Chem. Soc.  1999,  121:  4147 

4c Kumar P. Naidu V. Gupta P. Tetrahedron  2007,  63:  2745 

4d Gurjar MK. Murugaiah AMS. Krishna PR. Ramana CV. Chorghade MS. Tetrahedron: Asymmetry  2003,  14:  1363