A Practical Synthesis of a Potent δ-Opioid Antagonist: Use of a Modified Knorr Pyrrole Synthesis

A modified Knorr pyrrole reaction is described which may have practical benefits for the large-scale synthesis of SB-342219. The use of zinc to reduce a phenylhydrazone is replaced by the hydrogenation of the corresponding oxime to provide a common aminoketone intermediate. The modifications have practical benefit with respect to carrying out the reaction and isolating the product. A modified N-demethylation procedure is also described. The use of zinc to reduce an intermediate trichloroethylcarbamate is replaced with the aqueous hydrolysis of the corresponding 1-chloroethylcarbamate.