Two‐Step, One‐Pot Synthesis of Inosine, Guanosine, and 2′‐Deoxyguanosine O 6 ‐Ethers via Intermediate O 6 ‐(Benzotriazol‐1‐yl) Derivatives

A simple method for the etherification at the O 6 ‐position of silyl‐protected inosine, guanosine, and 2′‐deoxyguanosine is described. Typically, a THF solution of the silylated nucleoside is treated with 1 H ‐benzotriazol‐1‐yloxy‐tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and Cs 2 CO 3 under a nitrogen atmosphere. Conversion to the O 6 ‐(benzotriazol‐1‐yl) ethers occurs within about 10 min for inosine, and within about 60 min for guanosine and 2′‐deoxyguanosine. Then, for reaction with alcohols, the reaction mixture is evaporated and the O 6 ‐(benzotriazol‐1‐yl) ether is treated with Cs 2 CO 3 and an appropriate alcohol, at room temperature. On the other hand, for reaction with phenols, Cs 2 CO 3 and the appropriate phenol are added to the reaction mixture without evaporation, and the reaction is carried out at 70°C. Subsequently, workup, isolation, and purification lead to the requisite O 6 ‐alkyl or O 6 ‐aryl ethers in good to excellent yields. Curr. Protoc. Nucleic Acid Chem . 49:1.26.1‐1.26.16. © 2012 by John Wiley & Sons, Inc.