Process Improvement in the Production of a Pharmaceutical Intermediate Using a Reaction Calorimeter for Studies on the Reaction Kinetics of Amination of a Bromopropyl Compound

A synthetic process to produce a pharmaceutical intermediate, [3-(dimethylamino)propyl]triphenylphosphonium bromide (1), was established in the laboratory. Process safety evaluations did not show any severe problems. In order to scale up to plant scale, we simulated the reaction for both heat production and byproduct production profiles with kinetic parameters. The kinetic parameters were obtained by laboratory experiments and reaction calorimeter measurements. Under the established conditions, the production operated in a safe manner with high quality.