Reaction Safety:  An Improved Procedure for the Preparation of 1,3,4,12a-Tetrahydro-11H-[1,4]-oxanio[3,4-c][1,4]benzodiazepine-6,12-dione with Iron in Acetic Acid

This contribution describes the development of an improved scaleable process to prepare 1,3,4,12a-tetrahydro-11H-[1,4]-oxanio[3,4-c][1,4]benzodiazepine-6,12-dione, 2, in a safe and operationally simple procedure using iron powder in acetic acid. The original procedure being used to prepare initial quantities of this material also involves the use of iron with acetic acid. However, these original reaction conditions are not amenable to scale-up due to safety and operational issues. Reaction calorimetry is used to evaluate modifications to the original conditions that result in an improved procedure that has been developed and scaled to produce multikilogram amounts of material for initial development studies.