Synthetic route to isotopically labelled-oxamate

Article abstract of DOI:10.1002/jlcr.1876

Since none of the available methods was suitable for the synthesis of isotopically labelled oxamate, a new procedure has been developed in our laboratory, based on the known procedures, but with substantial modifications. The method is convenient and gives reproducibly 17% yield based on KCN used. The strategy is considered suitable for labelling oxamate with ¹⁵N and ¹³C or ¹⁴C when starting with labelled KCN and can be easily modified for the synthesis of ¹⁸O-carbonyl-labelled oxamate. Copyright 2011 John Wiley & Sons, Ltd. Synthesis route to sodium oxamate labelled with various isotopes has been proposed. Copyright

Full text of DOI:10.1002/jlcr.1876

Note
Received 7 December 2010,
Revised 21 December 2010,
Accepted 9 January 2011
Published online 25 April 2011 in Wiley Online Library
(
wileyonlinelibrary.com) DOI: 10.1002/jlcr.1876
Synthetic route to isotopically
labelled-oxamate
a
Ã
a
a
b
Agata Siwek, Nazar Trotsko, Monika Wujec, Rafa$ Kami n´ ski,
and Piotr Paneth
b
Since none of the available methods was suitable for the synthesis of isotopically labelled oxamate, a new procedure has
been developed in our laboratory, based on the known procedures, but with substantial modifications. The method is
convenient and gives reproducibly 17% yield based on KCN used. The strategy is considered suitable for labelling oxamate
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with N and C or C when starting with labelled KCN and can be easily modified for the synthesis of O-carbonyl-
labelled oxamate.
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Keywords: N-labelled oxamate; C-labelled oxamate; C-labelled oxamate; O-labelled oxamate
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13
14
18
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In the proposed method, sodium oxamate (4) was prepared in used. The product was characterized by comparison of its H
1
3
the three-step-synthesis as graphically illustrated in Scheme. and C NMR spectra with those of reference samples.
Thus, in the first step, ethyl cyanoformate (2) was prepared by Synthesis of sodium oxamate (4): the solution of (3) (4.8 mmol)
1
the procedure reported by Teplan et al. Next, in the acid- in 2% NaOH (10 mL) was heated on water bath for 50 min. Then,
catalyzed hydrolysis of nitrile group, ethyl oxamate (3) was solvent was evaporated and dry residue was recrystallized from
formed. The final product, (4), was obtained by base-catalyzed mixture water:ethanol (3:1) giving (4) with 72% yield based on
1
hydrolysis of (3).
(3) used. The product was characterized by comparison of its H
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3
All commercial reactants and solvents were purchased from and C NMR spectra with those of reference samples.
either Sigma-Aldrich or Lancaster and were used without further
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13
purification. H and C NMR spectra were recorded on a Bruker
Avance II Plus (250 MHz) spectrometer in DMSO-d
Acknowledgements
6
.
This work was supported by the grant NN204/1579/33 from the
Ministry of Science and Higher Education, Poland.
Reference
[
1] C. Teplan, D. Banfi, L. Otvos, Acta Chim. Acad. Sci. Hung. 1962,
3
Synthesis of ethyl cyanoformate (2): the mixture of ethyl
chloroformate (1) (30 mmol), potassium cyanide (20 mmol),
catalytic amount of sodium iodide and one drop of water was
heated in a sealed flask at 60–701C and the progress of the
4, 109.
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3
reaction was monitored by C NMR. After 24 h, analysis by NMR
spectra showed approximately 48% conversion (1) into (2)
based on the potassium cyanide used. The formation of (2) was
1
13
confirmed by comparison of its H and C NMR spectra with
those of reference samples.
Synthesis of ethyl oxamate (3): to the solution of pyrophos-
phoric acid (10.70 mmol) in dibutyl ether (9.5 mL) (2) (9.6 mmol)
was added and the reaction mixture was heated at 1151C for
1
.5 h with continuous stirring. Next, dibutyl ether was distilled
a
Department of Organic Chemistry, Faculty of Pharmacy, Medical University,
Lublin, Poland
under reduce pressure and the residue, after dissolving in
ethanol (5 mL), was neutralized with anhydrous potassium
carbonate. The obtained suspension was collected and the
supernate was evaporated in vacuum evaporator. Dry residue
was dissolved in ethyl acetate and filtered. The filtrate was
b
Institute of Applied Radiation Chemistry, Technical University of Lodz, Poland
*Correspondence to: Agata Siwek, Department of Organic Chemistry, Faculty of
Pharmacy, Medical University, Lublin, Poland.
evaporated to dryness giving (3) with 50% yield based on (2) E-mail: agata.siwek@am.lublin.pl
J. Label Compd. Radiopharm 2011, 54 344
Copyright r 2011 John Wiley & Sons, Ltd.