A detailed mechanistic investigation into the reaction of 3-methylpentanoic acid with Meldrum's acid utilizing online NMR spectroscopy.
A thorough investigation into the mechanism of the reaction of 3-methylpentanoic acid and Meldrum's acid using online NMR spectroscopy is reported. This study is an expansion of a previous analysis of this chemical transformation in the synthesis of an active pharmaceutical ingredient imagabalin. The 3-methylpentanoic acid analogue reveals similar behavior under the reaction conditions. Online NMR spectroscopy and offline characterization experiments reveal new information about the mechanism, providing conclusive spectroscopic evidence for the previously hypothesized dimer anhydride intermediate species 3-methylpentanoic anhydride as a productive intermediate. The presence of an acyl chloride intermediate species, 3-methylpentanoyl chloride, is also revealed for the first time in this synthesis. Copyright © 2015 John Wiley & Sons, Ltd.
Analytical Research and Development, Pfizer Worldwide Research and Development, 445 Eastern Point Road, Groton, CT, 06340, USA.|Department of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, WI, 53706, USA.
Anna L
AL
Dunn
Bruker UK Limited, Banner Lane, Coventry, CV4 9GH, UK.
Anna
A
Codina
Analytical Research and Development, Pfizer Worldwide Research and Development, 445 Eastern Point Road, Groton, CT, 06340, USA.
David A
DA
Foley
Bruker BioSpin, 15 Fortune Drive, Billerica, MA, 01821, USA.
Brian L
BL
Marquez
Analytical Research and Development, Pfizer Worldwide Research and Development, 445 Eastern Point Road, Groton, CT, 06340, USA.
Mark T
MT
Zell
NMR reaction monitoring; online NMR spectroscopy; reaction mechanism