Purification of Basic Compounds with Functionalized Silica Gel

Significance

Silica gel-supported phosphonic acid 4 was applied to cation-exchange SPE (solid-phase extraction) purification of basic compounds. Thus, for example, when the amide bond forming reaction of N-methylpiperazine (1) and an excess amount of N-Boc amino acid 2 was carried out with DIC and HOBt in CH₂Cl₂, the desired amide 3 was generated in the reaction mixture containing a side-product, N,N′-diisopropyl urea, unreacted HOBt, and 2. The crude reaction mixture was chromatographed on the functionalized silica gel 4 (eluent: MeOH) to elute the acidic and neutral components. Piperazine amide 3 was trapped by the acid 4 and was eluted by 0.7 M NH₃ in MeOH in 96% yield with 98% purity without loss of the acid-sensitive protecting groups.