Use of Dibutyl[¹⁴C]formamide as a Formylating Reagent in the <i>Vilsmeier</i>–<i>Haack</i> Reaction and Synthesis of a ¹⁴C‐Labeled Novel Phosphodiesterase‐4 (PDE‐4) Inhibitor

Abstract

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 ).