A Concise Synthesis of Racemic Lorcaserin

Bin Xu; Jincai Su; Jing Wang; Guo-Chun Zhou

doi:10.1071/CH15667

RESEARCH ARTICLE

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A Concise Synthesis of Racemic Lorcaserin

Bin Xu ^A ^C , Jincai Su ^A ^C , Jing Wang ^B ^D and Guo-Chun Zhou ^A ^D

+ Author Affiliations

- Author Affiliations

^A School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, Jiangsu, China.

^B College of Sciences, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.

^C These authors contributed equally to the work.

^D Corresponding authors. Email: wangjing@njau.edu.cn; gczhou@njtech.edu.cn

Australian Journal of Chemistry 69(7) 770-774 https://doi.org/10.1071/CH15667
Submitted: 21 October 2015 Accepted: 14 December 2015 Published: 28 January 2016

Abstract

We report herein the concise synthesis of racemic lorcaserin (±)-1, which is an anti-obesity drug. The synthetic route involved the key synthesis of an asymmetrical imide intermediate 11 and its efficient reduction. Imide 11 was synthesized directly by the reaction of nitrile 9 with acid 10. The reducing system of NaBH₄, AlCl₃, and trimethylsilyl chloride efficiently fulfilled the reduction of imide 11 to amine 8a, which could be converted to (±)-1 via Friedel–Crafts reaction as reported. This route afforded 69 % two-step yield of 8a from 9 via 11, and the concise synthesis of (±)-1 was completed in three steps. This route offers an alternative pathway to the synthesis of (±)-1 and its analogues.

References

[1] Prospective Studies Collaboration Lancet 2009, 373, 1083.
| Crossref | GoogleScholarGoogle Scholar | 19299006PubMed |

[2] J. C. Halford, E. J. Boyland, C. L. Lawton, J. E. Blundell, J. A. Harrold, Drugs 2007, 67, 27.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXitFGltLw%3D&md5=3ab6c44c3c8ceee71ad38ce279c7e1b4CAS | 17209663PubMed |

[3] W. J. Thomsen, A. J. Grottick, F. Menzaghi, H. Reyes-Saldana, S. Espitia, D. Yuskin, K. Whelan, M. Martin, M. Morgan, W. Chen, H. Al-Shamma, B. Smith, D. Chalmers, D. Behan, J. Pharmacol. Exp. Ther. 2008, 325, 577.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXlsVOjtrc%3D&md5=3d58b574ad06f3dc9164ce6bcf5b2ad3CAS | 18252809PubMed |

[4]    (a) J. Smith, B. Smith, World Patent WO 2003/086306 A2 2003.
      (b) B. M. Smith, J. M. Smith, J. H. Tsai, J. A. Schultz, C. A. Gilson, S. A. Estrada, R. R. Chen, D. M. Park, E. B. Prieto, C. S. Gallardo, D. Sengupta, W. J. Thomsen, H. R. Saldana, K. T. Whelan, F. Menzaghi, R. R. Webb, N. R. A. Beeley, Bioorg. Med. Chem. Lett. 2005, 15, 1467.
         | Crossref | GoogleScholarGoogle Scholar |
      (c) B. M. Smith, J. M. Smith, J. H. Tsai, J. A. Schultz, C. A. Gilson, S. A. Estrada, R. R. Chen, D. M. Park, E. B. Prieto, C. S. Gallardo, D. Sengupta, P. I. Dosa, J. A. Covel, A. Ren, R. R. Webb, N. R. A. Beeley, M. Martin, M. Morgan, S. Espitia, H. R. Saldana, C. Bjenning, K. T. Whelan, A. J. Grottick, F. Menzaghi, W. J. Thomsen, J. Med. Chem. 2008, 51, 305.
         | Crossref | GoogleScholarGoogle Scholar |
      (d) Q. Zhu, J. Wang, X. Bian, L. Zhang, P. Wei, Y. Xu, Org. Process Res. Dev. 2015, 19, 1263.
         | Crossref | GoogleScholarGoogle Scholar |

[5] (a) B. W. Burbaum, C. A. Gilson III, S. Aytes, S. A. Estrada, D. Sengupta, B. Smith, M. Rey, U. Weigl, World Patent WO 2005/019179 A2 2005.
(b) B. Smith, C. Gilson III, J. Schultz, J. Smith, World Patent WO 2005/003096 A1 2005.

[6] U. Weigl, F. Porstmann, C. Straessler, L. Ulmer, U. Koetz, World Patent WO 2007/120517 A2 2007.

[7] T. Gharbaoui, S. K. Tandel, Y. Ma, M. Carlos, J. R. Fritch, World Patent WO 2008/070111 A2 2008.

[8] X. Wang, X. J. Z. Li, Y. G. Li, Y. Gao, X. H. Lv, X. L. Shen, Z. Wang, X. L. Huang, China Patent CN 103333111 A 2013.

[9] M. K. Hargreaves, J. G. Pritchard, H. R. Dave, Chem. Rev. 1970, 70, 439.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE3cXkslKksrw%3D&md5=357680344f211c11e06d9190363b6ff7CAS |

[10] (a) D. Davidson, H. Skovronek, J. Am. Chem. Soc. 1958, 80, 376.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaG1cXlsFKgug%3D%3D&md5=8932109afa8e96a48eee35c17d2f915aCAS |
      (b) W. S. Durrell, J. A. Young, R. D. Dresdner, J. Org. Chem. 1963, 28, 831.
         | Crossref | GoogleScholarGoogle Scholar |
      (c) R. A. Slavinskaya, T. N. Sumarokova, T. A. Kovaleva, M. K. Nasirdinova, Zh. Org. Khim. 1982, 18, 2243.
      (d) V. A. Vinokurov, E. G. Gaevoi, L. A. Ryazanova, R. A. Karakhanov, Zh. Org. Khim. 1986, 22, 1783.

[11] (a) H. Zohreh, S. Peyman, A. Z. Mohammad, Y. Maryam, Synlett 2007, 812.
      (b) M. Nasr-Esfahani, M. Montazerozohori, N. Filvan, J. Serb. Chem. Soc. 2012, 77, 415.
         | Crossref | GoogleScholarGoogle Scholar |
      (c) M. M. Khodaei, E. Nazari, Tetrahedron Lett. 2012, 53, 2881.
         | Crossref | GoogleScholarGoogle Scholar |
      (d) J. Shang, A. Pourvali, J. R. Cochrane, C. A. Hutton, Aust. J. Chem. 2015, 68, 1854.
         | Crossref | GoogleScholarGoogle Scholar |

[12] A. Giannis, K. Sandhoff, Angew. Chem., Int. Ed. Engl. 1989, 28, 218.
| Crossref | GoogleScholarGoogle Scholar |

[13] Y. Qiu, F. Zhang, C. Zhang, Tetrahedron Lett. 2007, 48, 7595.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtFSiurjI&md5=51b569eedc57cd04eaf675c845c79f60CAS |

A Concise Synthesis of Racemic Lorcaserin

Abstract

References

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