Use of Dibutyl[14C]formamide as a Formylating Reagent in the Vilsmeier–Haack Reaction and Synthesis of a 14C-Labeled Novel Phosphodiesterase-4 (PDE-4) Inhibitor
✍ Scribed by Jonathan Z. Ho; Charles S. Elmore; Michael A. Wallace; Dan Yao; Matthew P. Braun; Dennis C. Dean; David G. Melillo; Cheng-yi Chen
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- German
- Weight
- 204 KB
- Volume
- 88
- Category
- Article
- ISSN
- 0018-019X
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✦ Synopsis
Abstract
A simple, high‐yielding synthesis of dibutyl[^14^C]formamide ([^14^C]DBF; 1) from ^14^CO~2~ was developed (Scheme 1): reaction of LiBEt~3~H and ^14^CO~2~ followed by aqueous workup gave H^14^CO~2~H in high yield. Conversion of the [^14^C]formic acid to 1 was effected by a standard carbodiimide coupling procedure. The utility of 1 as an alternative to dimethyl[^14^C]formamide ([^14^C]DMF) in alkylation reactions and in the [^14^C]Vilsmeier–Haack reaction was demonstrated for several substrates (Table 2). A ^14^C‐labeled phosphodiesterase‐4 (PDE‐4) inhibitor, [^14^C]‐2, was synthesized by application of this technology (Scheme 2).