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Updated: Aug 6, 2026

Optimization of the Ugi Reaction Using Parallel Synthesis and Automated Liquid Handling
Published on: November 11, 2008
An efficient, optimized synthesis of fentanyl and related analogs
Carlos A Valdez1, Roald N Leif1, Brian P Mayer1
1Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, California, United States of America; Forensic Science Center, Lawrence Livermore National Laboratory, Livermore, California, United States of America.
Abstract:
The alternate and optimized syntheses of the parent opioid fentanyl and its analogs are described. The routes presented exhibit high-yielding transformations leading to these powerful analgesics after optimization studies were carried out for each synthetic step. The general three-step strategy produced a panel of four fentanyls in excellent yields (73-78%) along with their more commonly encountered hydrochloride and citric acid salts. The following strategy offers the opportunity for the gram-scale, efficient production of this interesting class of opioid alkaloids.
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