Efficient Reductive N‐¹¹C‐Methylation Using Arylamines or Alkylamines and In Situ–Generated [¹¹C]Formaldehyde From [¹¹C]Methyl Iodide

Reductive N ‐ 11 C‐methylation using [ 11 C]formaldehyde and amines has been used to prepare N ‐ 11 C‐methylated compounds. However, the yields of the N ‐ 11 C‐methylated compounds are often insufficient. In this study, we developed an efficient method for base‐free reductive N ‐ 11 C‐methylation that is applicable to a wide variety of substrates, including arylamines bearing electron‐withdrawing and electron‐donating substituents. A 2‐picoline borane complex, which is a stable and mild reductant, was used. Dimethyl sulfoxide was used as the primary reaction solvent, and glacial acetic acid or aqueous acetic acid was used as a cosolvent. While reductive N ‐ 11 C‐methylation efficiently proceeded under anhydrous conditions in most cases, the addition of water to the reductive N ‐ 11 C‐methylation generally increased the yield of the N ‐ 11 C‐methylated compounds. Substrates with hydroxy, carboxyl, nitrile, nitro, ester, amide, and phenone moieties and amine salts were applicable to the reaction. This proposed method for reductive N ‐ 11 C‐methylation should be applicable to a wide variety of substrates, including thermo‐labile and base‐sensitive compounds because the reaction was performed under relatively mild conditions (70°C) without the need for a base.