Novel 2,2-bipyridine ligand for palladium-catalyzed regioselective carbonylation.
[reaction: see text] A palladium-catalyzed highly regioselective one-step carbonylation of 2,5-dibromo-3-methylpyridine is reported. A range of alkyl esters and amides can be prepared in good yield with better than 95:5 regioselectivity via this method. Key to the high regioselectivity for the formation aromatic amides is the introduction of a novel nonphosphine-based 2,2-bipyridine ligand. This novel reaction was scaled up smoothly in the plant to a 130-kg batch size and facilitated the delivery of bulk material for the clinical trials of Sch 66336, a candidate for oncologic treatments.
Wu
G G
GG
Chemical Process Research and Development, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA. george.wu@spcorp.com
Wong
Y
Y
Poirier
M
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D007202:Indicators and Reagents; D008024:Ligands; D010165:Palladium / Q000737:chemistry*; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry*; D003986:Dibenzocycloheptenes
D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D008024:Ligands; D010165:Palladium; D010880:Piperidines; D011725:Pyridines; C115354:lonafarnib; D003986:Dibenzocycloheptenes