Efficient DBU accelerated synthesis of 18F-labelled trifluoroacetamides

Antonio Bermejo Gómez; Miguel A Cortés González; Marvin Lübcke; Magnus J Johansson; Christer Halldin; Kálmán J Szabó; Magnus Schou

doi:10.1039/c6cc08535k

Efficient DBU accelerated synthesis of ¹⁸F-labelled trifluoroacetamides

Chem Commun (Camb). 2016 Nov 29;52(97):13963-13966. doi: 10.1039/c6cc08535k.

Authors

Antonio Bermejo Gómez¹, Miguel A Cortés González², Marvin Lübcke², Magnus J Johansson³, Christer Halldin⁴, Kálmán J Szabó², Magnus Schou⁵

Affiliations

¹ AstraZeneca Personalised Healthcare and Biomarkers, PET Centre at Karolinska Institutet, Karolinska Universitetssjukhuset Solna, R5:02, SE-171 76 Stockholm, Sweden. Magnus.Schou@astrazeneca.com and Department of Organic Chemistry, Stockholm University, Arrhenius Laboratory, SE-106 91 Stockholm, Sweden and Stockholm Brain Institute, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
² Department of Organic Chemistry, Stockholm University, Arrhenius Laboratory, SE-106 91 Stockholm, Sweden and Stockholm Brain Institute, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
³ CVMD iMed, Medicinal Chemistry AstraZeneca R&D, Mölndal, SE-431 83, Sweden.
⁴ Stockholm Brain Institute, Karolinska Institutet, SE-171 77 Stockholm, Sweden and Department of Clinical Neuroscience, Karolinska Institutet, S-17176 Stockholm, Sweden.
⁵ AstraZeneca Personalised Healthcare and Biomarkers, PET Centre at Karolinska Institutet, Karolinska Universitetssjukhuset Solna, R5:02, SE-171 76 Stockholm, Sweden. Magnus.Schou@astrazeneca.com and Stockholm Brain Institute, Karolinska Institutet, SE-171 77 Stockholm, Sweden and Department of Clinical Neuroscience, Karolinska Institutet, S-17176 Stockholm, Sweden.

PMID: 27844069
DOI: 10.1039/c6cc08535k

Abstract

Nucleophilic ¹⁸F-fluorination of bromodifluoromethyl derivatives was performed using [¹⁸F]Bu₄NF in the presence of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene). This novel procedure provided a diverse set of [¹⁸F]trifluoroacetamides in good to excellent radiochemical conversions. A mechanism where DBU acts as organomediator in this transformation is proposed.