Optimization of the Manufacturing Route to PF-610355 (1): Synthesis of Intermediate <b>5</b>

Dupont, Thomas; Fédou, Nicolas M.; Smith, J. D.; Twiddle, Steven J. R.

doi:10.1021/op300341n

Cited by 12 publications

(2 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Striving for better environmental and economic syntheses, chemists had achieved the optimization of many processes, including those of sildenafil citrate (Viagra) [68] and sertraline [69]. Today, innovative waste reduction methods are numerous and diverse, appearing in such areas as catalysis [70,71], catalyst recovery [72], solvent recovery [73] and optimization of work-up conditions [74]. Without the E factor metric, the field of green chemistry would not be where it currently is.…”

Section: Beyond the E Factor: Innovative Synthetic Methodsmentioning

confidence: 99%

The E Factor and Process Mass Intensity

Dicks

Hent

2014

SpringerBriefs in Molecular Science

View full text Add to dashboard Cite

The environmental (E) factor and process mass intensity (PMI) metrics are introduced and thoroughly analyzed. As indispensable green metrics widely applied throughout the chemical industry, the E factor and PMI are calculated for numerous industrial processes throughout the chapter. A perspective on waste in the context of academic research, industrial synthesis and reactivity within alternative reaction media highlights the importance of material recovery, in particular with regard to reaction solvents. The section on catalysis further expands on the question of waste reduction by considering several important points. Advantages of heterogeneous catalysis which include catalyst recycling and simple product isolation and purification are described. Issues and potential solutions encountered with homogeneous catalysts and potential solutions are also discussed. Finally, the biocatalytic synthesis of pregabalin sheds light on the notions of solvent recovery and water intensity. Limitations of the E factor (which include failure to address the nature of the waste produced) provide for an introduction to process mass intensity. After explaining the simple relationship between PMI and E factor, the chapter turns to the benefits of PMI as a more robust front-end approach for evaluating the material efficiency of a process. This idea is captured by considering the biocatalytic synthesis of Singulair. defined as "anything that is not the desired product" [1], in the years following its conception, the E factor metric has contributed to significant industrial waste reduction [2][3][4][5]. In tandem with atom economy, the E factor has provided the global view of synthetic efficiency. Typical industrial E factors first published by Sheldon (Table 3.1) [1] have enhanced understanding about the problem of waste and enabled various solutions to address it. Modern techniques are now starting to show potential in bypassing certain synthetic limitations once perceived in Sheldon's original conclusions. In recent years, efforts toward waste reduction have enabled many innovations such that the majority of process chemists today consider determining an E factor as essential to process development [6]. Keywords Intrinsic and Global E FactorsThe E factor approach to waste complements the atom economy metric because it offers both intrinsic and global evaluations of a synthetic process. The intrinsic method is one which Andraos calls the environmental impact factor based on molecular weight (E mw ) [7]. This metric is calculated as the ratio of the molecular weight of all by-products divided by the molecular weight of the desired product. The E factor based on mass (E factor) offers a global perspective and is calculated as the ratio of the total mass of all waste to the mass of the desired product [1]. Figure 3.1 outlines the calculations for both metrics in the context of a balanced stoichiometric reaction. From the conservation of mass law it is possible to derive simple mathematical relationships between the E factor me...

show abstract

Section: Beyond the E Factor: Innovative Synthetic Methodsmentioning

confidence: 99%

The E Factor and Process Mass Intensity

Dicks

Hent

2014

SpringerBriefs in Molecular Science

View full text Add to dashboard Cite

show abstract

“…Common tools that are routinely used in manufacturing include thermocouples and pressure sensors. Spectroscopic tools (e.g., near-infrared, − mid-infrared, − Raman, − UV − and NMR) − are utilized for increased analytical specificity (ability to monitor for the presence or disappearance of functional groups during the synthesis). By monitoring these specific functional groups, qualitative trending or quantitative assessment of the reaction component(s) levels is achieved.…”

Section: Introductionmentioning

confidence: 99%

Industry Perspectives on Process Analytical Technology: Tools and Applications in API Development

Chanda

Daly

Foley

et al. 2014

Org. Process Res. Dev.

148

114

View full text Add to dashboard Cite

The IQ Consortium reports on the current state of process analytical technology (PAT) for active pharmaceutical ingredient (API) development in branded pharmaceutical companies. The article uses an API process workflow (process steps from raw material identification through to finished API) to provide representative examples, including why and how the pharmaceutical industry uses PAT tools in API development. The use of PAT can improve R&D efficiency and minimize personnel hazards associated with sampling hazardous materials for in-process testing. Although not all steps or chemical processes are readily amenable to the use of the PAT toolbox, when appropriate, PAT enables reliable and rapid (real or near time) analyses of processes that may contain materials that are highly hazardous, transient, or heterogeneous. These measurements can provide significant data for developing process chemistry understanding, and they may include the detection of previously unknown reaction intermediates, mechanisms, or relationships between process variables. As the process becomes defined and understanding is gained through these measurements, the number of parameters suspected to be critical is reduced. As the process approaches the commercial manufacturing stage and the process design space is established, a simplification of the monitoring and control technology, as much as is practical, is desired. In many cases, this results in controls being either off-line, or if in situ control is required, the results from PAT are correlated with simple manufacturing measurements such as temperature and pressure.

show abstract

Lead Generation Approaches Delivering Inhaled β ₂ ‐Adrenoreceptor Agonist Drug Candidates

Stocks

Alcaraz²

2016

Methods and Principles in Medicinal Chemistry

View full text Add to dashboard Cite

Optimization of the Manufacturing Route to PF-610355 (1): Synthesis of Intermediate 5

Cited by 12 publications

References 17 publications

The E Factor and Process Mass Intensity

The E Factor and Process Mass Intensity

Industry Perspectives on Process Analytical Technology: Tools and Applications in API Development

Lead Generation Approaches Delivering Inhaled β ₂ ‐Adrenoreceptor Agonist Drug Candidates

Contact Info

Product

Resources

About

Optimization of the Manufacturing Route to PF-610355 (1): Synthesis of Intermediate 5

Cited by 12 publications

References 17 publications

The E Factor and Process Mass Intensity

The E Factor and Process Mass Intensity

Industry Perspectives on Process Analytical Technology: Tools and Applications in API Development

Lead Generation Approaches Delivering Inhaled β 2 ‐Adrenoreceptor Agonist Drug Candidates

Contact Info

Product

Resources

About

Lead Generation Approaches Delivering Inhaled β ₂ ‐Adrenoreceptor Agonist Drug Candidates