Beilstein J. Org. Chem.2017,13, 329–337, doi:10.3762/bjoc.13.36
could be synthesised by incorporation of CO2 from the supercritical solvent into the product.
Keywords: continuous flow; heterocycle; N-alkylation; self-optimisation; supercritical CO2; Introduction
N-alkylated amines are an important motif present in a range of pharmaceutically and industrially
alcohols using γ-Al2O3 with scCO2 as the solvent and employed self-optimisation [45][46] to explore the defined parameter space to effectively identify the highest yielding and optimal conditions in a relatively short timeframe.
Results and Discussion
To investigate our hypothesis that γ-Al2O3 with scCO2
). For this reaction, self-optimisation is important as multiple products were identified that could form in parallel; from 1 the possible products we expected to see were a mixture of piperidine (2a), N-methylpiperidine (2b), N- and O-methylated 1, as well as oligomers. We chose to target 2b only for
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Graphical Abstract
Scheme 1:
Target reaction – intramolecular cyclisation of 1 followed by N-methylation with methanol to yield ...
Beilstein J. Org. Chem.2017,13, 150–163, doi:10.3762/bjoc.13.18
recently described C(sp3)–H activation reaction to synthesise aziridines was used as a model reaction to demonstrate the methodology of developing a process model using model-based design of experiments (MBDoE) and self-optimisation approaches in flow. The two approaches are compared in terms of
experimental efficiency. The self-optimisation approach required the least number of experiments to reach the specified objectives of cost and product yield, whereas the MBDoE approach enabled a rapid generation of a process model.
Keywords: automated reaction system; C–H activation; design of experiments
; flow chemistry; process modelling; self-optimisation; Introduction
The development of manufacturing processes to produce functional molecules, such as pharmaceuticals or fine chemicals, often relies on experience and trial-and-error, rather than on mechanistic process models [1]. The only reason for
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Graphical Abstract
Figure 1:
A framework of closed-loop or self-optimisation combining smart DoE algorithms, process analytics, ...