Ethyl Dibromofluoroacetate (EDBFA)

Introduction

Over the last decades, fluorinated organic compounds have increasingly received great attention by the scientific community; in several scientific fields, from material science to medicine. Today, approximately 30% of all agrochemicals and 20% of all pharmaceuticals contain fluorine.[1] [2] The unique properties of fluorinated compounds are due to the high electronegativity of fluorine, the small size of fluorine, and the significant electrostatic character of the C–F bond.[3] The presence of a fluorine atom in organic compounds imparts several properties (basicity, lipophilicity, and metabolic stability) which in some cases enhance the drug-like properties of the molecule.[4]

A useful and commercially available reagent for fluorination of organic compounds is ethyl dibromofluoroacetate [EDBFA (1), Figure [1]].[5]

Figure 1 Ethyl dibromofluoroacetate (EDBFA)

Fluoroacetate 1 is a solid with a molecular weight of 263.89 g/mol, a boiling point of 173 °C, and a density of 1.92 g/cm³.[5] Derivatives of EDBFA such as compounds 2–6 (Scheme [1]) are also efficient reagents.[6] Replacement of one bromine atom in 1 by an azide generates a stereocenter, affording ethyl 2-azido-2-bromo-2-fluoroacetate (2). A two-step strategy is used to convert the ester moiety into the corresponding nitrile to give the 2,2-dibromo-2-fluoroacetonitrile (3).

Scheme 1 Synthesis of EDBFA derivatives

Using lithium borohydride as the reducing agent and trimethylborate, the ester moiety of 1 can be converted into an alcohol to give 2-azido-2-bromo-2-fluoroethan-1-ol (4).[6] [7] It can also be changed into a tertiary amide in the presence of dimethylaluminium chloride, affording 2-azido-2-bromo-N,N-diethyl-2-fluoroacetamide (5) or be transformed in the corresponding acyl chloride, via a three-step procedure, to afford 2-azido-2-bromo-2-fluoroacetyl chloride (6).

• References

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• 5 Data taken from the EUROPE Catalog, TCI Fine Chemicals 2012–2013.
• 6 David E, Couve-Bonnaire S, Jubault P, Pannecoucke X. Tetrahedron 2013; 69: 11039
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