A New, Direct Method for Selective Demethylation of N⁺-Methyl Quaternary Ammonium Iodides

Simple and selective one-pot replacement of the N-methyl group of tertiary amines by quaternization and demethylation with sodium sulfide or potassium thioacetate: an application to the synthesis of pergolide

“…9, 10 Our interest in the transformation of dihydrolysergol 1a into its congeners having different alkyl groups on the aliphatic nitrogen atom prompted us to seek for a simpler procedure for the exchange of the N-methyl group of 1a. In particular we were looking for a new procedure that would avoid some hassle encountered with the known methods, caused by the use of pyridine 5 or HMPA, 8 the need of a large excess of freshly prepared thioalkoxides, even in the best method to date, 9,10 and the long handling of hazardous intermediates.…”