96-well plate-to-plate gravity Fluorous Solid-Phase Extraction (F-SPE) for solution-phase library purification

Large particle size (125-210 μm) fluorous silica gel bonded with a -SiCH₂CH₂C₈F₁₇ stationary phase has been employed for gravity-driven fluorous solid-phase extraction (F-SPE) on two types of 96-well plates. A 1 or 0.75 g portion of fluorous silica is packed to each well of the 3.5-mL Ex-Blok and the 2.2-mL deep-well filtration plates, respectively. Up to 50 mg of reaction mixture is loaded and then eluted with a fluorophobic solvent (DMSO, DMF, or 85:15 DMF-H₂O). Products collected in 96-well receiving plates are directly concentrated on a GeneVac vacuum centrifuge. This simple and highly efficient plate-to-plate F-SPE technique has been demonstrated in the purification of four 96-compound libraries produced by scavenging reactions with 1-(perfluoroctyl)propyl isatoic anhydride (F-IA), amide coupling reactions with 2-chloro-4,6- bis[(perfluorooctyl)propyloxy]-1,3,5-triazine (F-CDMT) or 2,4-dichloro-6- (perfluorooctyl)-propyloxy-1,3,5-triazine (F-DCT), and Mitsunobu reactions with fluorous diethyl azodicarboxylate (F-DEAD) and triphenylphosphine (F-TPP). Approximately 80% of products in each library have greater than 85% purity after F-SPE without conducting chromatography.