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The Superbase Approach to Flurbiprofen: An Exercise in Optionally Site‐Selective Metalation
Author(s) -
Schlosser Manfred,
Geneste Hervé
Publication year - 1998
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/(sici)1521-3765(19981002)4:10<1969::aid-chem1969>3.0.co;2-o
Subject(s) - flurbiprofen , metalation , deprotonation , chemistry , carboxylation , superbase , stereochemistry , methylation , combinatorial chemistry , pharmacology , organic chemistry , medicine , biochemistry , catalysis , ion , gene
Abstract The structure of the antiinflammatory drug flurbiprofen [2‐(2‐fluoro‐4‐biphenylyl)propionic acid] presents a simple but challenging target to practice regiocontrolled assembly of molecular subunits through optionally site‐controlled metalation. The short and efficacious sequence shown leads to the final product: a four‐step, one‐pot conversion of 3‐fluorotoluene into 2‐fluoro‐4‐methylbiphenyl (79%), consecutive deprotonation and carboxylation (84%) of the benzylic methyl group, and, finally, α ‐deprotonation again followed this time by methylation (92%).