Industrial Quench Method for Triethylsilane, Featuring Process Development and Safety Measures

Abstract Safe process operation is critically important in the manufacture of active pharmaceutical ingredients. We employed an excess of triethylsilane (Et3SiH) as a reducing agent in the production of the dapagliflozin propanediol monohydrate. Although unreacted Et3SiH must be safely treated prior to disposal, no industrial quenching methods for Et3SiH have previously been reported. Accordingly, a safe treatment method using KOH in MeOH was developed. The quench reaction of Et3SiH under basic conditions was found to be exothermic and to evolve hydrogen. Therefore, measures to ensure safe plant-scale operations were required. The heat release profile during the quenching of Et3SiH was quantitatively evaluated. On the basis of these results, the quench reaction was controlled by adjusting the addition rate of KOH in MeOH. To safely vent the generated flammable hydrogen, it was necessary to maintain the oxygen concentration in the reactor headspace below the limiting oxygen concentration by using nitrogen purging. Implementation of these countermeasures successfully enabled the quenching of Et3SiH at the pilot scale.