Synthesis of 4-Halogenated 3-Fluoro-6-methoxyquinolines: Key Building Blocks for the Synthesis of Antibiotics

Thomas Flagstad; Mette T. Petersen; Daniel M. Hinnerfeldt; Michael Givskov; Thomas E. Nielsen

doi:10.1055/s-0034-1378554

Synthesis, Inhaltsverzeichnis

Synthesis 2014; 46(23): 3263-3267
DOI: 10.1055/s-0034-1378554

paper

Synthesis of 4-Halogenated 3-Fluoro-6-methoxyquinolines: Key Building Blocks for the Synthesis of Antibiotics

Thomas Flagstad

^aDepartment of Chemistry, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark Fax: + 45(4593)3968 eMail: ten@kemi.dtu.dk

,

Mette T. Petersen

^aDepartment of Chemistry, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark Fax: + 45(4593)3968 eMail: ten@kemi.dtu.dk

,

Daniel M. Hinnerfeldt

^aDepartment of Chemistry, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark Fax: + 45(4593)3968 eMail: ten@kemi.dtu.dk

,

Michael Givskov

^bDepartment of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark

^cSingapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, Singapore 637551, Singapore

,

Thomas E. Nielsen*

^aDepartment of Chemistry, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark Fax: + 45(4593)3968 eMail: ten@kemi.dtu.dk

^cSingapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, Singapore 637551, Singapore

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Abstract

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Abstract

A practical and scalable 4-step route is presented for the synthesis of 4-bromo-3-fluoro-6-methoxyoquinoline and 3-fluoro-4-iodo-6-methoxyoquinoline from readily available 2,4-dichloro-3-fluoroquinoline with an overall yield of 81–85%. Halogenated quinoline building blocks have found much use in antimicrobial drug discovery, and the method reported here would be useful for the synthesis of these compounds.

Key words

antibiotic - quinolone - fluorine - heterocycle - regioselectivity

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Referenzen

References

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15 A reviewer noted that this transformation might require flame-dried NaI. However, in our hands the reaction proceeded in 95% yield using NaI from the shelf.

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