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Synthesis 2021; 53(05): 961-970
DOI: 10.1055/a-1339-3227
paper

Late-Stage Transformation of Carboxylic Acids to N-Trifluoroethyl­imides with Trifluoromethyl Diazomethane

Xiao-Feng Qiu
a   National Engineering Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang, 330022, P. R. of China
b   Key Laboratory of Small Functional Organic Molecule, Ministry of Education, Jiangxi Normal University, Nanchang, Jiangxi 330022, P. R. of China
,
De-Yong Liu
a   National Engineering Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang, 330022, P. R. of China
,
Wen-Feng Zhang
a   National Engineering Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang, 330022, P. R. of China
,
Xiang-Guo Hu  ∗
a   National Engineering Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang, 330022, P. R. of China
b   Key Laboratory of Small Functional Organic Molecule, Ministry of Education, Jiangxi Normal University, Nanchang, Jiangxi 330022, P. R. of China
› Author AffiliationsWe thank the Outstanding Young Talents Funding of Jiangxi Province (20171BCB23039) for funding this research.
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Abstract

We report the first systematic evaluation of the reaction of trifluoromethyl diazomethane (2,2,2-trifluorodiazoethane, CF3CHN2) with drug-like molecules. We found our previous copper-catalyzed transformation of carboxylic acids to the corresponding N-trifluoro­ethylimides with CF3CHN2 and acetonitrile is well-suited for the late-stage modification of drug and drug-like acids. A procedure that enables the use of solid nitriles and nitriles with high boiling points as viable substrates is also disclosed.

Key words

N-trifluoroethylimides - trifluoromethyl diazomethane - late-stage functionalization - fluoroalkyl - copper - trifluoromethyl - 2,2,2-trifluorodiazoethane

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-1339-3227.
  • Supporting Information


Publication History

Received: 15 October 2020

Accepted after revision: 17 December 2020

Accepted Manuscript online:
17 December 2020

Article published online:
18 January 2021

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