Investigations into the synthesis of a nucleotide dimer via mechanochemical phosphoramidite chemistry.

Liquid-assisted mechanochemistry as a versatile approach for the coupling of a nucleoside phosphoramidite with a 5'-OH partially protected nucleoside has been investigated. Noted advantages over reported methods were a simplified reaction protocol, a drastic reduction in the use of toxic solvents, the facilitation of mechanochemical reactions through the improved mixing of solid reagents, and low hydrolytic product formation.