ORGN 616 |
Highly selective tandem SNAr reactions of 2,4-difluorobenzoic acid affords simple and rapid access to dissymmetrical 2,4-substituted benzoic
| Leland O. Weigel, Andrew Ratz, Perry Heath, William Trankle, Michael Rice, and Justin C. Smith. Eli Lilly and Company, Lilly Research Laboratories, Chemical Product Development and Research, Indianapolis, IN 46285-4813 |
| We will delineate the highly selective nature of SNAr reactions of 2,4-difluorobenzoic acid. Reaction of sodium (or potassium) 2,4-difluorobenzoate (1) with 1 equiv of an anion nucleophile (Nuc-, e. g. RO- or RS-) in polar aprotic media affords the product of ortho substitution (2, usually >98% selectivity). Addition of a second ’Nuc- to the reaction mixture affords dissymmetric 3 in high yield. This new methodology was developed as a “one-pot” reaction for the construction of Factor Xa drug candidate motifs (4). 
|
| |
|
New Reactions, Methodology, Heterocycles, Aromatics
8:00 PM-10:00 PM, Wednesday, August 25, 2004 Pennsylvania Convention Center -- Hall D, Poster
Division of Organic Chemistry
The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004
|