Profadol

Profadol is an opioid analgesic which was developed in the 1960s by Parke-Davis. It acts as a mixed agonist-antagonist of the μ-opioid receptor. The analgetic potency is about the same as of pethidine, the antagonistic effect is 1/50 of nalorphine.

Synthesis

The Knoevenagel condensation between 3'-Methoxybutyrophenone and Ethyl cyanoacetate gives. Conjugate addition of cyanide gives. Hydrolysis of both nitrile groups, saponification of the ester and decarboxylation gives the diacid, . Imide formation occurs upon treatment with methylamine giving 3--1-methyl-3-propylpyrrolidine-2,5-dione, . Reduction of the imide by lithium aluminium hydride gave . Demethylation completed the synthesis of Profadol.