<p>The standard methodology for the synthesis of oligonucleotides is the solid-phase method. Here, we report the first case of mechanochemistry being directly applied to the synthesis of a dinucleotide on a soluble support. While mechanochemistry eliminates the need to solubilise a supported oligomer in solution phase for phosphoramidite coupling, the support still confers the benefit of being able to purify the product by precipitation, or by simple liquid-liquid extractions as needed. Furthermore, this study also explores the use of mechanochemistry in the initial functionalisation of the ionic liquid support with a nucleoside monomer.</p>

<p>The standard methodology for the synthesis of oligonucleotides is the solid-phase method. Here, we report the first case of mechanochemistry being directly applied to the synthesis of a dinucleotide on a soluble support. While mechanochemistry eliminates the need to solubilise a supported oligomer in solution phase for phosphoramidite coupling, the support still confers the benefit of being able to purify the product by precipitation, or by simple liquid-liquid extractions as needed. Furthermore, this study also explores the use of mechanochemistry in the initial functionalisation of the ionic liquid support with a nucleoside monomer.</p>