PRACTICAL SYNTHESIS OF 8-ALPHA-AMINO-2,6-DIMETHYLERGOLINE - AN INDUSTRIAL PERSPECTIVE

8 alpha-Amino-2,6-dimethylergoline is the key intermediate for the syn thesis of a number of ergot derivatives under clinical development, Th ey are structurally related to the better known lysergic acid and its derivative, the diethylamide (LSD). The use of lysergic acid or its is omer, paspalic acid, both of which are readily available by fermentati on on an industrial scale, as a starting material for the synthesis of 8 alpha-amino-2,6-dimmethylergoline appears to be the obvious choice as the basic structural elements already exist. Whereas the transforma tion of the acid function to the amino moiety proceeded under well-est ablished conditions, the introduction of the single methyl group posed a major challenge to the industrial chemist. Various methodologies ar e available to solve this problem, and the approach that involves dire ct metalation and methylation is found to be most suitable for up-scal ing to multiton quantities. The importance of using on-line monitoring techniques (FTIR) in process research and development will be exempli fied by this report.