3 research outputs found
Scale-Up Investigation of the Continuous Phase-Transfer-Catalyzed Hypochlorite Oxidation of Alcohols and Aldehydes
The use of bleach to oxidize alcohols
with the aid of a phase-transfer
catalyst (PTC) offers several benefits over traditional oxidants:
low material cost, mild reaction conditions, and no metallic waste.
Mass transport limitations often dictate overall reaction rates of
such PTC reactions, and continuous-flow reactors with superior mass
and heat transport performance are consequently used to enhance their
rates. Three PTC hypochlorite oxidation reactions are chosen to illustrate
scaling of PTC reactions from microfluidic to mesoscale systems [Corning
Low Flow Reactor (LFR) and Advanced Flow Reactor (AFR)]. The successful
scaling from microliters per hour in microreactors to intermediate
milliliters per minute without sacrificing mass transport performance
leads to significant increases in production rate and constitutes
an efficient flow reactor scaling approach. The production rate increases
up to 700 times in the scaling process from a spiral microreactor
to the LFR and then to the AFR
Design, Execution, and Analysis of Time-Varying Experiments for Model Discrimination and Parameter Estimation in Microreactors
Time-varying,
or dynamic, experiments can produce richer data sets
than sequences of steady-state experiments using less material and
time. A case study demonstrating this concept for microreactor experiments
is presented. Beginning with five kinetic model candidates for the
reaction of phenylisocyanate with <i>t</i>-butanol, an initial
dynamic experiment showed that two of the five models gave a similar
quality of fit to the experimental data, whereas the remaining three
gave significantly poorer fits. Next an optimal experiment was designed
to discriminate between the remaining two models. This drove the two
models to differ significantly in quality, leaving a single model
and a set of kinetic parameter values that adequately described the
data. This method can be applied to future kinetic studies to reduce
material use and experimental time while validating a dynamic model
of the physics and chemical kinetics
Development of a Multi-Step Synthesis and Workup Sequence for an Integrated, Continuous Manufacturing Process of a Pharmaceutical
The development and operation of the synthesis and workup steps
of a fully integrated, continuous manufacturing plant for synthesizing
aliskiren, a small molecule pharmaceutical, are presented. The plant
started with advanced intermediates, two synthetic steps away from
the final active pharmaceutical ingredient, and ended with finished
tablets. The entire process was run on several occasions, with the
data presented herein corresponding to a 240 h run at a nominal throughput
of 41 g h<sup>–1</sup> of aliskiren. The first reaction was
performed solvent-free in a molten condition at a high temperature,
achieving high yields (90%) and avoiding solid handling and a long
residence time (due to higher concentrations compared to dilute conditions
when run at lower temperatures in a solvent). The resulting stream
was worked-up inline using liquid–liquid extraction with membrane-based
separators that were scaled-up from microfluidic designs. The second
reaction involved a Boc deprotection, using aqueous HCl that was rapidly
quenched with aqueous NaOH using an inline pH measurement to control
NaOH addition. The reaction maintained high yields (90–95%)
under closed-loop control despite process disturbances