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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
A straightforward, one-pot protocol for the preparation of libraries of 2-oxazolines
Stefano Crosignani1, Dominique Swinnen
1Serono Pharmaceutical Research Institute, 14 Chemin des Aulx, 1228 Plan-les-Ouates, Geneva, Switzerland. stefano.crosignani@serono.com
Abstract:
A practical protocol for the parallel synthesis of 2-oxazolines using polymer-supported reagents is described. Polymer-supported Mukaiyama reagent is used to couple a carboxylic acid with an amino alcohol, giving a beta-hydroxyamide, which is then cyclized in situ using either polymer-supported sulfonyl chloride resin or polymer-bound 2-fluoropyridinium triflate. Both 2,4-disubstituted and 2,4,5-trisubstituted 2-oxazolines are obtained in high yields and excellent purities after a simple resin filtration and solvent evaporation routine.
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