New preparations of the N-methyl-D-aspartate receptor antagonist, 4-(3-phosphonopropyl)-2-piperazinecarboxylic acid (CPP)

Abstract Two new methods to ensure selective alkylation of the N 4 of 2-piperazinecarboxylic acid to give 4-(3-phosphonopropyl)-2-piperazinecarboxylic acid ( CPP, 1 ) are reported. CPP can be conveniently prepared using a copper chelate to selectively protect the N 1 position during alkylation. A second procedure uses methyl-4-BOC-1-CBZ-2-piperazinecarboxylate 5 as a versatile intermediate, which was further elaborated to CPP.