Multigram Synthesis of C₄/C₅ 3,3-Difluorocyclobutyl-Substituted Building Blocks

Abstract

An approach for the multigram synthesis of 3,3-difluorocyclobutyl-substituted building blocks (including carboxylic acid, amines, alcohols, azide, trifluoroborate ketone) is described. It is shown that, in most cases, ethyl 3,3-difluorocyclobutanecarboxylate is a convenient common synthetic intermediate to obtain the target derivatives. For preparation of 3,3-difluorocyclobutanol or -cyclobutanone, an alternative pathway via reaction of dichloroketene and tert-butyl or benzyl vinyl­ ether should be applied.

Key words

cycloalkanes - organofluorine compounds - fluorination - conformational restriction - lead-oriented synthesis

• References

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