This study addresses critical challenges in the production of ethyltriphenylphosphonium bromide (ETPB) by evaluating the use of bio-based solvents within a biorefinery framework to improve both yield and sustainability, leading to the selection of isopropanol based on its efficiency, superior solvation capacity, lower environmental impact, and higher safety profile than traditional volatile organic compounds (VOCs). Data includes Solvent screening, experimental data using the chosen solvent (isopropanol), calculations of process, health and environmental metrics, surrogate models and cross-validation, optimized operating conditions via genetic algorithm, and analytical analysis from FTIR, Raman, and 1H-RMN.