How to Convert a Walk-in Hood into a Manufacturing Facility: Demonstration of a Continuous, High-Temperature Cyclization to Process Solids in Flow

An intramolecular thermal cyclization protocol was developed in a flow reactor to take advantage of the high pressures and temperatures that are easily obtained in small scale autoclave reactors that have been modified to handle slurries. This reactor was equipped with a fill/empty pumping system to enable easy and nearly complete transfer of slurries. The reaction conditions were designed to take advantage of the insolubility of the product in order to separate it from residual starting material by filtration after short reaction times. Recycling of the filtrate maximized the yield and throughput while minimizing decomposition. Recycles were accomplished using a strip to dryness protocol that was easily performed in a rotary evaporator. This new equipment set was designed with lab-hood manufacturing in mind, a minimized footprint, and the system was completely automated for charging, emptying, rinsing, and reacting. Additional efforts for quick screening and alternate modes of addition were also investig...