Organic-Fluorous Phase Switches: A Fluorous Amine Scavenger for Purification in Solution Phase Parallel Synthesis

Abstract

The synthesis of the fluorous amine scavenger [(C(6)F(13)CH(2)CH(2))(3)SiCH(2)CH(2)CH(2)](2)NH and its successful application in the automated solution phase parallel synthesis of a urea library are described. Ureas were made by robotic synthesis from organic amines and excess isocyanates. The amine scavenger reacts with excess isocyanate, and the fluorous tag serves to solubilize the resulting adduct in the fluorous phase so it can be removed by fluorous-organic extraction. Organic urea products are isolated in high yields and purities after liquid-liquid extraction. Preliminary biological evaluation shows that several of the ureas have ion channel modulation abilities. In contrast to polymer and ionic quenching methods, the fluorous quench works whether the product is soluble or insoluble in the reaction medium, and ionizable functional groups are tolerated in the products.