A Scalable Synthesis of 2‑(1,2,4-Oxadiazol-3-yl)propan-2-amine
Hydrobromide Using a Process Safety-Driven Protecting Group Strategy

Likhite, Nachiket; Lakshminarasimhan, Thirumalai; H. V. Ramana Rao, Mallem; Shekarappa, Vijaykumar; Sidar, Somprabha; Subramanian, Varadharajan; Fraunhoffer, Kenneth
J.; Leung, Simon; Vaidyanathan, Rajappa

doi:10.1021/acs.oprd.6b00145.s001

op6b00145_si_001.pdf (327.17 kB)

A Scalable Synthesis of 2‑(1,2,4-Oxadiazol-3-yl)propan-2-amine Hydrobromide Using a Process Safety-Driven Protecting Group Strategy

journal contribution

posted on 2016-06-15, 17:50 authored by Nachiket Likhite, Thirumalai Lakshminarasimhan, Mallem H. V. Ramana Rao, Vijaykumar Shekarappa, Somprabha Sidar, Varadharajan Subramanian, Kenneth J. Fraunhoffer, Simon Leung, Rajappa Vaidyanathan

A safe and scalable synthesis of 2-(1,2,4-oxadiazol-3-yl)propan-2-amine hydrobromide is described. A process safety-driven synthetic strategy was employed for the selection of thermally stable compounds en route to the target 1,2,4-oxadiazole. Application of process safety principles and tools for predicting the stability of process streams, isolated compounds, and for defining optimum reaction parameters are discussed in detail. The effect of protecting groups on the thermal stability of isolated intermediates is also highlighted.