Synthesis of 2-and 3-trifluoromethylmorpholines: useful building blocks for drug discovery

2- and 3-Trifluoromethylmorpholines were prepared in racemic and optically active forms. The synthesis commenced from the commercially available 2-trifluoromethyloxirane. The elaborated procedures were scalable, and the products were obtained in multigram quantities. The obtained compounds were comprehensively characterized by crystallographic analysis, fluorescence measurements, solubility, pK(a), logD parameters, and clearance rate. The potential of the synthesized amines as the building blocks for drug discovery is thus demonstrated. (C) 2013 Elsevier Ltd. All rights reserved.