Formation of Trifluoroacetylated Ephedrine During the Analysis of a Pseudoephedrine-Formaldehyde Adduct by TFAA Derivatization Followed by GC-MS

Abstract:  (+)-Pseudoephedrine reacts with formaldehyde to form (4 S ,5 S )-3,4-dimethyl-5-phenyloxazolidine. Gas chromatography–mass spectrometry (GC-MS) analysis after the reaction of this oxazolidine with excess trifluoroacetic acid anhydride (TFAA) shows predominantly N , O- bis(trifluoroacetyl)pseudoephedrine with some of the monotrifluoroacetylated derivative. In addition, variable amounts of N , O- bis(trifluoroacetyl)ephedrine were detected by GC-MS. N , O- bis(trifluoroacetyl)ephedrine was not detected upon trifluoroacetylation of the source (+)-pseudoephedrine, and nuclear magnetic resonance analysis of the (4 S ,5 S )-3,4-dimethyl-5-phenyloxazolidine showed no evidence of the (4 R ,5 S ) isomer. This suggests that the N ,O-bis(trifluoroacetyl)ephedrine is formed by epimerization during the TFAA derivatization and GC-MS analysis of the pseudoephedrine-formaldehyde adduct.