Synthesis and Purification of Fentanyl Analogs

All chemicals were purchased from commercial suppliers and used as received. 2,2,2-Trichloroethoxycarbonyl chloride (Troc-Cl), ammonium hydroxide and dichloromethane were purchased from Sigma-Aldrich (St. Louis, MO.). Potassium bicarbonate was purchased from Acros Organics (Westchester, PA.). Autosampler vials were purchased from Agilent Technologies (Santa Clara, CA.). Fentanyl and acetylfentanyl were synthesized using published protocols [11 (link)]. Thin layer chromatography (TLC) was used to monitor the production of amine-containing intermediates leading to the synthesis of fentanyl and acetylfentanyl using Merck 60-F254 sheets and detection accomplished with UV light (λ = 254 nm) in conjunction with CAM [36 (link), 37 (link)] and iodine vapor [38 (link), 39 (link)]. All fentanyls as well as the Troc-norfentanyl and Troc-noracetylfentanyl standards were purified by flash column chromatography using a Biotage Isolera purification system.