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. 2017 May 9;53(38):5334-5337.
doi: 10.1039/c7cc01407d.

From [11C]CO2 to [11C]amides: a rapid one-pot synthesis via the Mitsunobu reaction

S Bongarzone  1 , A Runser  1 , C Taddei  1 , A K Haji Dheere  1 , A D Gee  1
Affiliations

From [11C]CO2 to [11C]amides: a rapid one-pot synthesis via the Mitsunobu reaction

S Bongarzone et al. Chem Commun (Camb). .

Abstract

A novel amide synthesis methodology is described using amines, CO2 and Grignard reagents and Mitsunobu reagents. The method was applied to carbon-11 radiochemistry to label amides using cyclotron-produced [11C]CO2. The synthetic utility of the one-pot labelling methodology was demonstrated by producing [11C]melatonin. The incorporation of [11C]CO2 into [11C]melatonin was 36% - determined by radioHPLC 2 min post [11C]CO2 delivery.

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Figures

Scheme 1
Scheme 1. Different approaches available for the preparation of [11C]amides using Grignard reagents or boronic esters.
Scheme 2
Scheme 2. Radiosynthetic approach to radiolabelled [11C]ureas and [11C]amides (this work) from cyclotron-produced [11C]CO2.
Scheme 3
Scheme 3. Reaction conditions: [11C]CO2 was bubbled in a solution of 7 (32 μmol, 1 equiv.), DBU (10 equiv.) in MeCN (160 μL) at room temperature. Then, the reaction mixture was heated (50 °C) for 30 seconds. Mitsunobu reagents (8 equiv.) in MeCN (100 μL) were added and stirred for 10 s. D (8 equiv., 3.0 M in Et2O) was added. The reaction was quenched after 1 min.
See this image and copyright information in PMC

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