Mechanistic insight into the oxazoline decomposition of DFC-M, a synthetic intermediate of florfenicol.


Analytical Research & Development, Merck & Co. Inc., Rahway, NJ, 07065, United States. Electronic address: [Email]


2-(dichloromethyl)-5[4-(methylsulfonyl)-phenyl]-4-(fluoromethyl)-oxazoline (DFC-M, 1) is a key oxazoline-containing intermediate in commercial process for the synthesis of Florfenicol (3), a marketed broad spectrum veterinary antibiotic. DFC-M was not stable in solution due to the presence of oxazoline moiety, which provided further hindrance for analytical sample preparation and HPLC analysis. Hence, the mechanistic study on the in-solution degradation of DFC-M was carried out via online and offline UPLC-HR-ESI-MS as well as in-situ NMR, and the degradation pathways were proposed. This mechanistic information, together with the follow-up solution stability study, provided crucial information regarding the solution handling and mobile phase selection for DFC-M analysis during commercial processing.


Florfenicol,Florfenicol amine,NMR,On-column decomposition,Oxazoline,UHPLC-HR-ESI-MS,