Chemoselective three-phase hydrogenation of an Ombrabulin nitro-stilbene intermediate in a continuous-flow mobile platform

Fixed Bed Continuous Hydrogenations in Trickle Flow Mode: A Pharmaceutical Industry Perspective

“…This allows the system to be used as an early development tool when developing chemistry for transfer to pilot plant, with the tube-to-particle diameter being a key consideration (see section 3.4 for a discussion on the importance of consideration of tube-to-particle ratio). 19,122,123 The H-Cube (including later H-Cube Pro, Figure 2a and H-Cube Midi, Figure 22b) is operated with upward flow (flooded bed reactors); Figure 2d shows the flow path for the H-Cube, H-Cube pro, and H-Cube Midi. The H-Cube Maxi (Figure 2c) can be operated as either a trickle bed or flooded bed reactor.…”

“…80,84 The use of monolithic packing in trickle bed reactors would give a D t /D p ratio of 1; Bayer/Sanofi and Santolubes Manufacturing LLC have reported on their use. 122,158 Monoliths can allow mass-transfer enhancement over a fixed bed of catalyst particles. 159−162 Choosing the D t /D p ratio defines the particle sizes used within a reactor, for example, for reactors with an ID of 3 mm, at a D t /D p of 10, the maximum particle size is 300 μm, and at a D t /D p of 15, the maximum particle size is 200 μm.…”

“…The introduction of the ThalesNano H-Cube (Figure a) in the mid 2000s (at the American Chemical Society August 2004 meeting) allowed fixed bed reactors to be conveniently utilized by many pharmaceutical companies, and now, they would be considered a common tool in many laboratories. ,,,− The H-Cube has had a 2-fold effect since its release: It has given researchers access to higher pressures and temperatures, than usually achievable in batch vessels. Many pharmaceutical companies have pressure and temperature limits on their laboratory batch vessels, which echo the companies’ pilot plant and manufacturing vessel capabilities. ,,− It has become a common laboratory tool and has introduced many researchers to the field of flow chemistry. …”

“…It has given researchers access to higher pressures and temperatures, than usually achievable in batch vessels. Many pharmaceutical companies have pressure and temperature limits on their laboratory batch vessels, which echo the companies’ pilot plant and manufacturing vessel capabilities. ,,− …”

“…ThalesNano supply a range of prepacked catalysts (CatCarts) for the H-Cube in addition to empty 3 mm internal diameter (ID) reactors, which can be self-packed by researchers. This allows the system to be used as an early development tool when developing chemistry for transfer to pilot plant, with the tube-to-particle diameter being a key consideration (see section for a discussion on the importance of consideration of tube-to-particle ratio). ,, …”