Synthesis of N-protected (S)-prolinonitrile

Two accesses to N-Boc-(S)-prolinonitrile (tert-butyl (S)-2-cyanopyrrolidine-1-carboxylate) from (S)-l-proline, namely, a three-step procedure that involves synthesis of intermediate N-Boc-l-Pro-NH2 and a six-step procedure that excludes the synthesis of this intermediate, were compared. The second approach despite more steps is easier to accomplish and provides the target compound in 47% yield based on the starting l-proline. © 2025 Elsevier B.V., All rights reserved.