A new method for production of chiral 2-aryl-2-fluoropropanoic acids using an effective kinetic resolution of racemic 2-aryl-2-fluoropropanoic acids

Molecules. 2012 Jun 14;17(6):7356-78. doi: 10.3390/molecules17067356.

Abstract

We report a new method for the preparation of chiral 2-aryl-2-fluoropropanoic acids, including 2-fluoroibuprofen, a fluorinated analogue of non-steroidal anti-inflammatory drugs (NSAIDs), by the kinetic resolution of racemic 2-aryl-2-fluoropropanoic acids using enantioselective esterification. By applying pivalic anhydride (Piv2O) as a coupling agent, bis(α-naphthyl)methanol [(α-Np)2CHOH] as an achiral alcohol, and (+)-benzotetramisole (BTM) as a chiral acyl-transfer catalyst, a series of racemic 2-aryl-2-fluoropropanoic acids were kinetically separated to afford the optically active carboxylic acids and the corresponding esters with good to high enantiomeric excesses. This technology can provide a convenient approach to furnish the chiral α-fluorinated drugs containing quaternary carbons at the α-positions in the 2-aryl-2-fluoropropanoic acid structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Catalysis
  • Kinetics
  • Nuclear Magnetic Resonance, Biomolecular
  • Propionates / chemical synthesis*
  • Propionates / chemistry
  • Solvents / chemistry
  • Stereoisomerism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Propionates
  • Solvents