Using NPS chromatography to monitor mesylation reactions

Using nonporous silica (NPS) chromatography, mesylation reactions with unhi ndered and hindered amines were studied as proton scavengers. During reacti on monitoring it is important to conduct sensitive and fast analyses. To op timally control the reaction quick feedback is necessary. The NPS proved to be highly suitable. When unhindered amines are used to remove the proton, the S(N)2 mesylate reaction was observed to take place, followed by the S(N )1 reaction to form the quaternary salt. The S(N)1 reaction did not occur w hen the sterically hindered dicyclohexylamine was used. Liquid chromatograp hy/mass spectrometry confirmed this process and was used to identify the fi nal products when various amines were used as proton scavengers. This study confirmed that dicyclohexylamine is the preferred proton scavenger if one desires to obtain a stoichiometric amount of mesylate.