A novel use of catalytic zinc-hydroxyapatite columns for the selective deprotection of N-tert-butyloxycarbonyl (BOC) protecting group using flow chemistry

Abstract

The development of a single step flow process for the deprotection of the common protecting group tert-butyloxycarbonyl (BOC) is presented. Conventional BOC deprotection methods can require up to 24 h to fully deprotect compounds and may require cleanup due to undesired side products [1]. Long reaction times, high temperature, and undesired destruction of other protecting groups or the compound itself, have been reported in alternative methods presented recently in the literature [2]. The process presented herein allows for near quantitative and selective deprotection of the BOC protecting group in 30 min at 150 °C in flow using a zinc-hydroxyapatite (Zn-HAP) column. A selection of nineteen examples with diverse functionalities were used to demonstrate the application of this catalyst in flow. The products of the reactions were analyzed by HPLC, LC-MS and CE to determine the yield and purity. In comparison to the standard deprotection methods our process yields a clean, fast and selective method to deprotect N-Boc products and yields the desired corresponding free amine products. Of the nineteen compounds, nine transformations resulted in clean products (≥90 % ). One of these products was tested for racemization and the product remained enantiopure.