Continuous,on-demand generation and separation of diphenylphosphoryl azide |
| |
| Authors: | Stephen C Born Chelsea ER Edwards Benjamin Martin Klavs F Jensen |
| |
| Institution: | 1. Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139, USA;2. Novartis Pharma AG, Chemical and Analytical Development, Fabrikstrasse 14, 4002 Basel, Switzerland |
| |
| Abstract: | Diphenylphosphorylazide (DPPA) has been synthesized in microfluidics with near-100% yield in sub-3 minute residence time, affordably, and with a process design that minimizes hazards associated with hydrazoic acid (HN3) production. A pilot-plant scale continuous process for the on-demand synthesis of diphenylphosphoryl azide (DPPA) that can readily be integrated with subsequent transformations was designed, built, and validated. Using Corning's Low Flow reactor system coupled to a membrane separator and in-line Fourier Transform Infrared (FTIR), DPPA was safely produced at a rate of 1?mol/hr as a 2.0?M anhydrous toluene stream. Continuous FTIR was able to reliably monitor product quality, purity and concentration, showcasing the ease and utility of this continuous flow process for manufacturing common, safe pharmaceutical precursors. |
| |
| Keywords: | Continuous azide synthesis Diphenylphosphoryl azide Continuous flow chemistry Tetrabutyl ammonium bromide |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
