Solving Formulation Issues: Preventing Premature Hydrolysis and Tar Byproduct Formation from Residual Methanol and >0.5% LOD During Bosentan Coupling
Residual methanol in Dimethyl 2-(2-Methoxyphenoxy)Malonate acts as a competitive nucleophile during the coupling stage, disrupting the intended reaction pathway. When combined with a loss on drying (LOD) exceeding 0.5%, premature hydrolysis occurs, generating malonic acid derivatives that polymerize into tar byproducts under thermal stress. This side reaction is exacerbated by the
