Synthesis of (-)-oseltamivir by using a microreactor in the curtius rearrangement

Hayato Ishikawa, Bojan P. Bondzic, Yujiro Hayashi

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

A microflow reaction of the Curtius rearrangement by using trimethylsilyl azide as an azide source, followed by trapping of the generated isocyanate with a nucleophile was established, which is safe, inexpensive, and suitable for large-scale synthesis. By this flow reaction in the Curtius rearrangement and recrystallization of the late-stage acetamide intermediate the third-generation synthesis of (-)-Oseltamivir has been established, which is efficient, practical, and safe. A safe and efficient total synthesis of (-)-Oseltamivir has been developed by using the Curtius rearrangement with a microflow system, which avoids the isolation of a hazardous and potentially explosive intermediate. In addition, the product, possessing an acetamide group, was easily purified by recrystallization. Thus, this procedure can be scaled up as an industrial process.

Original languageEnglish
Pages (from-to)6020-6031
Number of pages12
JournalEuropean Journal of Organic Chemistry
Issue number30
DOIs
Publication statusPublished - 2011 Oct
Externally publishedYes

Keywords

  • Antiviral agents
  • Process chemistry
  • Synthesis design
  • Tamiflu
  • Total synthesis

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry

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