Optimization of Ullmann Reaction Step in the Synthesis of Sertindole

Abstract:

5-chloro-1-(4- fluorophenyl)-indole is a key intermediate of sertindole. It can be synthesized from 4-fluoro-bromobenzene and 5-chloroindole by Ullmann reaction, but this step required significant optimization to improve yield and reproducibility for the purity processes of the syntheses that have been disclosed are quite complicated and the reaction proceeds usually can’t go to completion. The Ullmann reaction step in the synthesis of sertidole was improved by using purified 5-chloroindole, suitable catalyst and solvent. A viable kilo-scale synthesis of the 5-chloro-1-(4- fluoro phenyl)-indole was described. Simple workup, economical, high yields and purity of product are some advantages of this method.

• Periodical: Advanced Materials Research (Volumes 236-238)
• Pages: 2594-2597
• DOI: https://doi.org/10.4028/www.scientific.net/AMR.236-238.2594
• Online since: May 2011
• Authors: Wen Li, Xiao Qing Ma, Jiang He Yu
• Keywords: 5-Chloro-1-(4-Fluorophenyl) Indole, Sertindole, Synthesis, Ullmann Reaction

References

[1] J.K. Perregaard, U.S. Patent 4710500. (1987)

[2] P. Jens, S. Torben, U.S. Patent 5112838. (1992)

[3] B. Sommer, Michael, WO patent 9851685. (1998)

[4] J.Z. Venezia, M.V. Padova, F. C. Padova, U.S. Patent 20050101788. (2005)

[5] J.Q. Li, X.J. Ye and L.Y. Huang, CN patent 101362748A. (2009) In Chinese

[6] J.Q. Li, X.J. Ye and L.Y. Huang, CN patent 101591330A. (2009) In Chinese

[7] Z. Jacopo, V. Marco, HK patent 1080855 A1. (2010)

[8] P. Jens, A. Jorn and P.B. Klaus: J. Med. Chem. Forum Vol. 35 (1992), pp.1092-1101