A process for commercial manufacture of the dual D
2-
2receptor agonist sibenadet hydrochloride has been developed.The process relies upon introduction of operationally simplechemistry at the final stages where two key intermediates arereacted to assemble the final molecule, isolated by crystallization. A nine-stage sequence for synthesis of the key aminehydrochloride intermediate was developed, and modificationsto the original process are described. Major strategic improvements were made in definition of the final route to the "sidechain" precursor molecule, the second key intermediate, hingingaround a thiyl radical addition and subsequent high-yieldingtelescoped processes for synthesis of this highly crystallinebenzoate ester. Development of these chemistries is discussed,together with some issues surrounding definition of the finalvalidated commercial processes.