5. From batch to continuous chemical synthesis – a toolbox approach

Plouffe, Patrick; Macchi, Arturo; Roberge, Dominique M.

doi:10.1515/9783110289169.141

Cited by 2 publications

(3 citation statements)

References 30 publications

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“…Continuous-flow chemistry has gained much attention in the past decade because of its several advantages over batch systems. − Continuous manufacturing has been applied in petrochemical and bulk chemical industries for a number of years. However, the synthesis of APIs is usually carried out in batch or semibatch reactors becaues of their similarities to reactions in R&D laboratories which are carried out in test tubes, round-bottom flasks, or closed vessels.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, in a typical flow setup, the reactions are conducted in microtubing reactors. − This allows highly exothermic reactions to be carried out in a safer manner as only a small volume of different reagents can mix in the reactor during the synthesis, mitigating safety issues such as overpressure or overheating, which may occur while using large batch reactors. Furthermore, the usage of microtubing reactors enhances heat and mass transfer, allowing for a shorter residence time compared with a batch reactor. − …”

Section: Introductionmentioning

confidence: 99%

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Olefin Metathesis in Continuous Flow Reactor Employing Polar Ruthenium Catalyst and Soluble Metal Scavenger for Instant Purification of Products of Pharmaceutical Interest

Toh

Patrzałek

Nienałtowski

et al. 2021

ACS Sustainable Chem. Eng.

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In recent years, the development of continuous-flow reactors has attracted growing attention from the synthetic community. Moreover, findings in the precise control of the reaction parameters and improved mass/heat transfer have made the flow setup an attractive alternative to batch reactors, both in academia and industry, enabling safe and easy scaling-up of synthetic processes. Even though a majority of the pharmaceutical industry currently rely on batch reactors or semibatch reactors, many are integrating flow technology because of easier maintenance and lower risks. Herein, we demonstrate an operationally simple flow setup for homogeneous ring-closing metathesis, which is applicable to the synthesis of active pharmaceutical ingredients precursors or analogues with high efficiency, low residence time, and in a green solvent. Furthermore, through the addition of a soluble metal scavenger in the subsequent step within the flow system, the level of ruthenium contamination in the final product can be greatly reduced (to less than 5 ppm). To ensure that this method is applicable for industrial usage, an upscale process including a 24 h continuous-flow reaction for more than 60 g of a Sildenafil analogue was achieved in a continuous-flow fashion by adjusting the tubing size and flow rate accordingly.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Olefin Metathesis in Continuous Flow Reactor Employing Polar Ruthenium Catalyst and Soluble Metal Scavenger for Instant Purification of Products of Pharmaceutical Interest

Toh

Patrzałek

Nienałtowski

et al. 2021

ACS Sustainable Chem. Eng.

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“…The application of a flow chemistry setup would permit precise temperature and pressure control as well as efficient heat transfer (Figure ). These features should allow us to scale up this transformation under safe reaction conditions while furnishing products in shorter reaction times …”

mentioning

confidence: 99%

Difluorocarbene Addition to Alkenes and Alkynes in Continuous Flow

2016

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The first in-flow difluorocarbene generation and addition to alkenes and alkynes is reported. The application of continuous flow technology allowed for the controlled generation of difluorocarbene from TMSCF3 and a catalytic quantity of NaI. The in situ generated electrophilic carbene reacts smoothly with a broad range of alkenes and alkynes, allowing the synthesis of the corresponding difluorocyclopropanes and difluorocyclopropenes. The reaction is complete within a 10 min residence time at high reaction concentrations. With a production flow rate of 1 mmol/min, continuous flow chemistry enables scale up of this process in a green, atom-economic, and safe manner.

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5. From batch to continuous chemical synthesis – a toolbox approach

Cited by 2 publications

References 30 publications

Olefin Metathesis in Continuous Flow Reactor Employing Polar Ruthenium Catalyst and Soluble Metal Scavenger for Instant Purification of Products of Pharmaceutical Interest

Olefin Metathesis in Continuous Flow Reactor Employing Polar Ruthenium Catalyst and Soluble Metal Scavenger for Instant Purification of Products of Pharmaceutical Interest

Difluorocarbene Addition to Alkenes and Alkynes in Continuous Flow

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