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DOI: 10.1055/s-2004-829111
Further Metalations and Functionalizations of Chloro-, Bromo- and Iodo(trifluoromethyl)pyridines
Publication History
Publication Date:
23 June 2004 (online)
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Abstract
In accordance with the concept of regioexhaustive functionalization, both 3-chloro-2-(trifluoromethyl)pyridine and 2-bromo-6-(trifluoromethyl)pyridine were converted each time into the three possible carboxylic acids (1, 4 and 5 and 6, 9 and 12, respectively). 2-Bromo-4-(trifluoromethyl)pyridine, 2-bromo-5-(trifluoromethyl)pyridine, 2-iodo-4-(trifluoromethyl)pyridine and 4-iodo-2-(trifluoromethyl)pyridine were selectively deprotonated and subsequently carboxylated at the respective 3-positions thus affording the acids 13-16. Finally, the N-pivaloyl-protected 2-amino-3-chloro-5-(trifluoromethyl)pyridine was deprotonated at the 4-position and the intermediate trapped with iodine and benzaldehyde to provide, after amide cleavage, the aminopyridines 17 and 18.
Key words
halogen/metal permutation (‘exchange’) - halogen migration - metalations - lithium diisopropylamide - pyridines - site selectivity
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