Design of selective 1-ethyl-2-nitromethylenepyrrolidine hydrogenation for pharmaceuticals production

The peculiarities of 1-ethyl-2-nitromethylenepyrrolidine (ENMP) hydrogenation over Pd/C catalyst were studied. Two routes of ENMP conversion resulting in 1-ethyl-2-aminomethylpyrrolidine (EAMP) and side products formation were found out. It was shown that the side reaction is the ENMP hydrolysis. This reaction proceeds via the acid-base mechanism and is accelerated by EAMP, producing the basic medium. The new method of EAMP preparation by ENMP hydrogenation in presence of CO 2 was proposed. The kinetic peculiarities of this process were studied and parameters determining the EAMP selectivity were clarified. The role of CO 2 in selective ENMP hydrogenation was studied using IR, 1 H and 13 C NMR methods. It was found that the reversible interaction of EAMP with CO 2 produces the intermolecular salt of EAMP carbamic acid and thus prevents ENMP hydrolysis by maintaining the neutral pH of the reaction medium. The catalytic setup for the ENMP hydrogenation and the new method of EAMP separation and purification, which provides the high-purity EAMP for medicines synthesis, have been developed.