Synthesis 2018; 50(24): 4949-4957
DOI: 10.1055/s-0037-1610237
paper
© Georg Thieme Verlag Stuttgart · New York

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

Kostiantyn P. Melnykov
a  Enamine Ltd., Chervonotkatska Street 78, Kyiv 02094, Ukraine
b  Taras Shevchenko National University of Kyiv, Volodymyrska Street 64, Kyiv 01601, Ukraine   Email: S.V.Ryabukhin@gmail.com
,
Dmitriy S. Granat
a  Enamine Ltd., Chervonotkatska Street 78, Kyiv 02094, Ukraine
,
Dmitriy M. Volochnyuk
a  Enamine Ltd., Chervonotkatska Street 78, Kyiv 02094, Ukraine
c  Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanska Street 5, Kyiv 02660, Ukraine
,
a  Enamine Ltd., Chervonotkatska Street 78, Kyiv 02094, Ukraine
b  Taras Shevchenko National University of Kyiv, Volodymyrska Street 64, Kyiv 01601, Ukraine   Email: S.V.Ryabukhin@gmail.com
,
a  Enamine Ltd., Chervonotkatska Street 78, Kyiv 02094, Ukraine
b  Taras Shevchenko National University of Kyiv, Volodymyrska Street 64, Kyiv 01601, Ukraine   Email: S.V.Ryabukhin@gmail.com
› Author Affiliations
Further Information

Publication History

Received: 25 June 2018

Accepted after revision: 16 July 2018

Publication Date:
20 August 2018 (online)


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.

Supporting Information

 
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