Continuous Extraction of 2-Chloroethyl isocyanate for 1-(2-chloroethyl)-3-cyclohexylurea Purification

This study details the development of simulation-aided design, development, and successful operation of a continuous liquid-liquid extraction platform made with 1.5 mm tubing for the extraction of 2-chloroethyl isocyanate, an important reagent in the synthesis of cancer drugs. Preliminary solvent screening was carried out with partition coefficient calculations to determine solvents of interest. Next, batch and flow extraction experiments of 2-chloroethyl isocyanate in 2-methyl tetrahydrofuran and water were conducted to estimate extraction parameters. Following parameter estimation, experimental and model values for K_La were determined in the range of 1.13×10^-3 to 36.0×10^-3 s^-1. Simulations of the extraction of 2-chloroethyl isocyanate were found to agree with experimental data resulting in a maximum efficiency of 77% and percent extraction of 69% for the continuous platform. Finally, model selection and discrimination was implemented for design space generation with experimental and model determined K_La values to guide lab-scale operation.