A New Method for Production of Chiral 2-Aryl-2-fluoropropanoic Acids Using an Effective Kinetic Resolution of Racemic 2-Aryl-2-fluoropropanoic Acids

作者：Tengeiji Atsushi; Shiina Isamu^*

来源：Molecules, 2012, 17(6): 7356-7378.

DOI：10.3390/molecules17067356

• kinetic resolution
• asymmetric esterification
• 2-aryl-2-fluoropropanoic acids
• fluorinated drugs
• 2-fluoroibuprofen
• ibuprofen

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 (Piv(2)O) as a coupling agent, bis(alpha-naphthyl) methanol [(alpha-Np)(2)CHOH] 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 alpha-fluorinated drugs containing quaternary carbons at the a-positions in the 2-aryl-2-fluoropropanoic acid structure.

• 出版日期2012-6