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.

Shcherbatiuk A. V.; Shyshlyk O. S.; Yarmoliuk D. V.; Shishkin O. V.; Shishkina S. V.; Starova V. S.; Zaporozhets O. A.; Zozulya S.; Moriev R.; Kravchuk O.; Manoilenko O.; Tolmachev A. A.; Mykhailiuk P. K.
Tetrahedron 2013, 69 (19), 3796-3804
DOI: 10.1016/j.tet.2013.03.067