206193-53-5Relevant academic research and scientific papers
Ortho-directed lithiation studies of 4-chloropicolinanilide : Introduction of functional groups at C-3 and their elaboration to chain extended derivatives via carbon-carbon bond formation
Nora De Souza, Marcus V.,Dodd, Robert H.
, p. 811 - 827 (2007/10/03)
An improved synthesis of 4-chloropicolinanilide (3) is presented. Treatment of 3 with lithium diisopropylamide (LDA) in THF, followed by addition of an electrophile (methyl iodide, iodine, carbon dioxide, trimethylstannyl chloride), gave exclusively the products of C-3 substitution (respectively, the 3-methyl-, 3-iodo, 3-carboxylic acid and 3-trimethylstannyl derivatives of 3). Further treatment of the 3-methyl derivative (7) with carbon dioxide or ethyl bromoacetate produced the one- and two-carbon homologues of 4-chloroquinolinanilide (8 and 9, respectively). The palladium acetate-catalyzed reaction of 4-chloro-3-iodopicolinanilide (10) with various unsaturated derivatives (trimethylsilylacetylene, tri-n-butyl(vinyl)tin, styrene, acrylonitrile, methyl acrylate) afforded the corresponding C-3 cross-coupled products in 70-80% yield. Reaction of 10 with allyl alkoxide, followed by treatment of the product (17) with tri-n-butyltin hydride, provided the 2-methylfuro[3,2-c]pyridine derivative (18) in 85% yield.
