A new method for production of chiral 2-aryl-2-fluoropropanoic acids using an effective kinetic resolution of racemic 2-aryl-2-fluoropropanoic acids.
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.
Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan.
Atsushi
A
Tengeiji
Isamu
I
Shiina
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis*; D002384:Catalysis; D007700:Kinetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D011422:Propionates / Q000138:chemical synthesis* / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011422:Propionates; D012997:Solvents