Patent Watch

April 21, 2014

Synthesize high-purity 2,2-difluoroethylamines in two steps. N. Lui and S. Antons disclose a process for producing 2,2-difluoroethylamines that are key intermediates in the synthesis of agrochemicals, particularly insecticides. A related patent that covers 2,2-difluoroethylamine synthesis by amide hydrogenation has been reviewed previously (Turner, K. Org. Process Res. Dev. 2013, 17, 15–27).

In this patent, the only examples cover the synthesis of difluoroethylamine 4 in a two-step process. The first step is the condensation of amine 1 with aldehyde 2 that proceeds without any other reagents. After the water produced in the reaction is removed with MgSO4 and the solvent is evaporated, crude imine product 3 is distilled. The isolated yield is 93.8% with 99.5% purity. 

Synthesis of difluoroethylamine 4

In the second step, 3 is hydrogenated with H2/Raney Ni or NaBH4. These procedures give 4 in 96.7% yield with 99% purity and 86% yield with 93% purity, respectively. 1H NMR data for 3 and 4 are provided.

In summary, the two-step process gives high yields of very pure products without complex workup and purification procedures. (Bayer Cropscience AG [Monheim, Germany]. US Patent 8,637,673, Jan. 28, 2014; Keith Turner)