Catalytic Reduction of Amides Avoiding LiAlH4OR B2H6

Dodds, Deborah L.; Cole‐Hamilton, David J.

doi:10.1002/9781118354520.ch01

Cited by 14 publications

(16 citation statements)

References 48 publications

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“…For the established reagents, such as LiAlH 4 , diborane complexes, DIBAL and Red-Al the issues of safety, atom efficiency and waste disposal are still major concerns and barriers to adoption. 64 Given the wealth of amide syntheses and ubiquity of amines in drug substances, efficient and sustainable amide reduction is still very much an underused methodology in the pharmaceutical industry.…”

Section: Amide Reductions Avoiding Lialh 4 and Diboranementioning

confidence: 99%

“…The natural progression to minimize the waste is to move to the more atom economical strategy of hydrogenation. 64 Of the 766 in scope amide reduction reactions, 111 were hydrogenation based (over 26 articles) when monoselective imide reductions were removed. The majority of these were heterogeneous reactions that required high temperatures and pressures and are in general intolerant of a wide range of active functionality.…”

Section: Scheme 4 Schemementioning

confidence: 99%

“…A promising indicator for the future use of dimethylisosorbide is that it has recently been assessed in a solvent selection guide. 197 Propylene carbonate is a valuable polar aprotic solvent which has low viscosity and high dielectric constant (64) which allows for excellent solvation properties. Propylene carbonate also has a very favourable toxicological profile as no significant toxic effects were observed in rats fed propylene carbonate, exposed to the vapour, or to the neat liquid.…”

Section: Viable Replacements For Polar Aprotic Solventsmentioning

confidence: 99%

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Key Green Chemistry research areas from a pharmaceutical manufacturers’ perspective revisited

et al. 2018

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Section: Amide Reductions Avoiding Lialh 4 and Diboranementioning

confidence: 99%

Section: Scheme 4 Schemementioning

confidence: 99%

Section: Viable Replacements For Polar Aprotic Solventsmentioning

confidence: 99%

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Key Green Chemistry research areas from a pharmaceutical manufacturers’ perspective revisited

et al. 2018

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“…Compared with the deaminative process, the deoxygenative hydrogenation of amides produces the corresponding higher amines and H 2 O. From a synthetic point of view, this methodology is more interesting as it allows in principle the efficient formation of new C-N bonds via N-acylation and subsequent hydrogenation 54 . For these reasons, in 2005 the ACS Green Chemistry Institute and members of the so-called Pharmaceutical Roundtable named this transformation as a "dream reaction" for future developments in process chemistry 3,4 .…”

Section: Development Of Homogeneous Catalystsmentioning

confidence: 99%

Homogeneous and heterogeneous catalytic reduction of amides and related compounds using molecular hydrogen

et al. 2020

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Catalytic hydrogenation of amides is of great interest for chemists working in organic synthesis, as the resulting amines are widely featured in natural products, drugs, agrochemicals, dyes, etc. Compared to traditional reduction of amides using (over)stoichiometric reductants, the direct hydrogenation of amides using molecular hydrogen represents a greener approach. Furthermore, amide hydrogenation is a highly versatile transformation, since not only higher amines (obtained by CO cleavage), but also lower amines and alcohols, or amino alcohols (obtained by C-N cleavage) can be selectively accessed by fine tuning of reaction conditions. This review describes the most recent advances in the area of amide hydrogenation using H 2 exclusively and molecularly defined homogeneous as well as nanostructured heterogeneous catalysts, with a special focus on catalyst development and synthetic applications. T he development of green and sustainable methods is a central focus of modern organic synthesis and its applications in various areas of the chemical industry. In this respect, many reduction reactions, traditionally employing stoichiometric amounts of metal hydrides with inherent low atom efficiency 1 , can be favorably replaced by catalytic hydrogenations. In fact, the combination of molecular hydrogen and catalysts does not only allow avoiding formation of waste products 2 , it also opens the door to clean transformations based on renewable energies as the conversion of solar or wind energy to "green" hydrogen is likely to be implemented in the coming years. Among the many reduction reactions known, amide hydrogenation can be encountered as one of the most desired considering the importance of the derived amines in several branches of chemical industry. In fact, since the start of the Green Chemistry Institute Pharmaceutical Roundtable in the United States in 2005, several projects aimed to the achievement of a practical amide hydrogenation methodology have been supported 3,4. The long-term interest of the pharmaceutical industry in this specific transformation is explained by the fact that it ideally affords structurally complex amines, present in many of the currently employed drugs. Furthermore, amines are also in bulk and fine chemicals used in the manufacture of plastics, textiles, surfactants, dyes, and many more 5. Amides play a central role in the chemistry of life, as they are the key elements to generate peptides and proteins from amino acid monomers. At the same time, they are present in artificial

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“…One of the objectives in organic synthesis is the production of complex polyfunctional bioactive drug molecules with high purity. In recent years, the usage of catalysts based on rare earth metals is common for the synthesis of active pharmaceutical ingredients (API) in the pharmaceutical industry. − One such process that is finding more and more applications in the synthesis of biologically active compounds is olefin metathesis. − It enables the formation of new C–C double bonds and relies mainly on the complexes of two transition metals, ruthenium and molybdenum. − The development of modern catalysts, especially Grubbs and Hoveyda–Grubbs second-generation Ru-complexes (Figure ), as well as their polar analogues that are easier to be separated after the reaction (like StickyCat PF 6 , Figure ), has significantly facilitated the synthesis of even complex organic compounds and enabled a substantial reduction of the catalyst loading . Nevertheless, the reliance on heavy metals for organic synthesis potentially leads to metal contamination because traditional purification methods like column chromatography and recrystallization is inefficient in purifying complex polyfunctional chemical substances such as APIs in downstream processes .…”

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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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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Catalytic Reduction of Amides Avoiding LiAlH₄OR B₂H₆

Cited by 14 publications

References 48 publications

Key Green Chemistry research areas from a pharmaceutical manufacturers’ perspective revisited

Key Green Chemistry research areas from a pharmaceutical manufacturers’ perspective revisited

Homogeneous and heterogeneous catalytic reduction of amides and related compounds using molecular hydrogen

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

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