Synthesis of 2,2-difluoro-2-arylethylamines as fluorinated analogs of octopamine and noradrenaline

Abstract

A series of 2,2-difluoro-2-arylethylamines was synthesized as fluorinated analogs of octopamine and noradrenaline with the expectation of bioisosteric OH/F exchanges. The syntheses of these compounds were performed by a Suzuki–Miyaura cross-coupling reaction of 4-(bromodifluoroacetyl)morpholine with aryl boronic acids to produce the intermediate 2,2-difluoro-2-arylacetamides, followed by transformation of difluoroacetamide to difluoroethylamine.

Keywords

• difluoroacetamide
• fluorine analogue
• suzuki–miyaura coupling
• octopamine
• noradrenaline