Application of continuous flow processes in the synthesis of fentanyl opioids

• Ano de defesa: 2022
• Autor(a) principal: Vaz, Artur de Lara Lima
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Biblioteca Digitais de Teses e Dissertações da USP
• Palavras-chave em Português: Continuous flow; Fentanila; Fentanyl; Fluxo contínuo; Organic synthesis; Síntese orgânica
• Link de acesso: https://www.teses.usp.br/teses/disponiveis/60/60138/tde-28082023-162107/

Fentanyl and fentanyl analogues are fully synthetic opioids of the phenylpiperidine class discovered by Janssen et al. in 1959, found to be the most potent anesthetics known so far, reaching tens of hundreds of times the analgesic potency of morphine. In this work, the preparation of fentanyl, and fentanyl analogues, under continuous flow conditions was investigated. This was accomplished by the multi-step preparation under common batch methodologies, by adaptation of such methods to continuous flow settings, and development of novel synthetic strategies, involving reactions such as azaMichael addition, reductive amination, catalytic hydrogen transfer deprotection, and others. It is shown that the methodologies here discussed were successful in the preparation of fentanyl and its precursors, as well as of remifentanil, a high potent, fast-acting anesthetic, with great clinical importance. The synthetic methodology here investigated may be of interest in the up-scaling of the preparation of this class of synthetic opioids by means of continuous flow techniques.