Brazilian Journal of Pharmaceutical Sciences (Jun 2023)

Continuous flow Aza-Michael reaction for preparing the fast-acting synthetic opioid drug Remifentanil

  • Artur de Lara Lima Vaz,
  • João Luis Callegari Lopes,
  • Giuliano Cesar Clososki

DOI
https://doi.org/10.1590/s2175-97902023e22764
Journal volume & issue
Vol. 59

Abstract

Read online

Abstract Remifentanil is a modern fentanyl analogue with ultrashort-action granted by an esterase-labile methyl propanoate chain. Here, we present the development of a continuous flow methodology for the key N-alkylation step of remifentanil preparation in a biphasic, “slug-flow” regime. We screened parameters under microwave-assisted reactions, translated conditions to flow settings, and obtained remifentanil under 15-min residence time in a 1-mL microreactor, with a space-time yield of 89 mg/mL·h and 94% yield.

Keywords