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Monatshefte für Chemie - Chemical Monthly

, Volume 146, Issue 9, pp 1541–1545 | Cite as

Optimization of stereoselective Michael addition of 2-(pentan-3-yloxy)acetaldehyde to N-[(Z)-2-nitroethenyl]acetamide with the aid of design of experiments

  • Viktória Hajzer
  • Pavel Alexy
  • Attila Latika
  • Július Durmis
  • Radovan ŠebestaEmail author
Original Paper

Abstract

Stereoselective Michael addition of 2-(pentan-3-yloxy)acetaldehyde to N-[(Z)-2-nitroethenyl]acetamide is a key step in the organocatalytic synthesis of oseltamivir, active ingredient in the anti-influenza drug Tamiflu. Several important reaction parameters were analyzed by the help of design of experiments and optimum reaction conditions were found. These conditions led to improvements of the reaction outcomes.

Graphical abstract

Keywords

Organocatalysis Michael addition Oseltamivir Design of experiment Alkyloxyacetaldehyde Nitroalkene 

Notes

Acknowledgments

This work was supported by Slovak Research and Development Agency, grant no. APVV-0067-11.

Supplementary material

706_2015_1486_MOESM1_ESM.docx (495 kb)
Supplementary material 1 (DOCX 495 kb)

References

  1. 1.
    Aleman J, Cabrera S (2013) Chem Soc Rev 42:774CrossRefGoogle Scholar
  2. 2.
    Ricci A (2014) ISRN organic chemistry. Article ID 531695Google Scholar
  3. 3.
  4. 4.
    Farina V, Brown JD (2006) Angew Chem Int Ed 45:7330CrossRefGoogle Scholar
  5. 5.
    Magano J (2009) Chem Rev 109:4398CrossRefGoogle Scholar
  6. 6.
    Magano J (2011) Tetrahedron 67:7875CrossRefGoogle Scholar
  7. 7.
    Shibasaki M, Kanai M, Yamatsugu K (2011) Isr J Chem 51:316CrossRefGoogle Scholar
  8. 8.
    Shibasaki M, Kanai M (2008) Eur J Org Chem p 1839Google Scholar
  9. 9.
    Ishikawa H, Suzuki T, Hayashi Y (2009) Angew Chem Int Ed 48:1304CrossRefGoogle Scholar
  10. 10.
    Ishikawa H, Suzuki T, Orita H, Uchimaru T, Hayashi Y (2010) Chem Eur J 16:12616CrossRefGoogle Scholar
  11. 11.
    Mukaiyama T, Ishikawa H, Koshino H, Hayashi Y (2013) Chem Eur J 19:17789CrossRefGoogle Scholar
  12. 12.
    Zhu S, Yu S, Wang Y, Ma D (2010) Angew Chem Int Ed 49:4656CrossRefGoogle Scholar
  13. 13.
    Weng J, Li Y-B, Wang R-B, Lu G (2012) Chem Cat Chem 4:1007Google Scholar
  14. 14.
    Rehák J, Huťka M, Latika A, Brath H, Almássy A, Hajzer V, Durmis J, Toma S, Šebesta R (2012) Synthesis 44:2424CrossRefGoogle Scholar
  15. 15.
    Hajzer V, Latika A, Durmis J, Šebesta R (2012) Helv Chim Acta 95:2421CrossRefGoogle Scholar
  16. 16.
    Lazić ŽR (2005) Design of experiments in chemical engineering: a practical guide. Wiley-VCH Verlag GmbH & Co. KGaA, WeinheimGoogle Scholar
  17. 17.
    O’Brien M, Denton R, Ley SV (2011) Synthesis p 1157Google Scholar
  18. 18.
    Aggarwal VK, Staubitz AC, Owen M (2006) Org Process Res Dev 10:64CrossRefGoogle Scholar
  19. 19.
    Veum L, Pereira SRM, van der Waal JC, Hanefeld U (2006) Eur J Org Chem p 1664Google Scholar
  20. 20.
    Denmark SE, Butler CR (2008) J Am Chem Soc 130:3690CrossRefGoogle Scholar
  21. 21.
    Glasnov TN, Tye H, Kappe CO (2008) Tetrahedron 64:2035CrossRefGoogle Scholar
  22. 22.
    Massari L, Panelli L, Hughes M, Stazi F, Maton W, Westerduin P, Scaravelli F, Bacchi S (2010) Org Process Res Dev 14:1364CrossRefGoogle Scholar
  23. 23.
    Marigo M, Wabnitz TC, Fielenbach D, Jørgensen KA (2005) Angew Chem Int Ed 44:794CrossRefGoogle Scholar
  24. 24.
    Hayashi Y, Gotoh H, Hayashi T, Shoji M (2005) Angew Chem Int Ed 44:4212CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  1. 1.Synkola Ltd.BratislavaSlovakia
  2. 2.Department of Plastics and Rubber, Faculty of Chemical and Food TechnologySlovak Technical UniversityBratislavaSlovakia
  3. 3.Department of Organic Chemistry, Faculty of Natural SciencesComenius University in BratislavaBratislavaSlovakia

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