In summary, a method suitable for the synthesis of the highly sensitive ac4C-containing RNAs has been developed. The method uses SoM for the protection of exo-amino groups of nucleobases, and SoA for linking RNA to solid support. Deprotection and cleavage can be achieved under non-nucleophilic conditions using fluoride. Because fluoride is compatible with a wide range of functional groups in organic molecules, the method is predicted to be suitable for the synthesis of RNAs containing many other sensitive groups as well. Many sensitive RNAs exist in nature. Malfunction of them is related to many human diseases. A method for chemical synthesis of these RNAs is expected to open doors to many projects aimed to answer a wide range of fundamental biological questions related to sensitive RNA modifications.