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The technology-driven world we live in seems to become more complex, more quickly, with every passing day. At a systems level, higher education has responded to the needs of a complex world by promoting specialism, and encouraging deep-dive learning in relatively narrow fields. Specialist expertise is to be valued, but developing the new sustainable processes

Sodium Azide-Sonic Boom Boy

Last week I was in Madrid running our chemical development and scale up course. I met a great group of people, one of whom worked at Dynamit Nobel. During a coffee break we struck up a conversation about (of all things) azides, in particular sodium azide. Fairly quickly we both discovered that we had no

Cleaning Up Micelle Chemistry

For the past decade I have been intrigued by the emergence of micelle technology and its ability to enable many organic reactions in water, but perplexed about why the reactions work as effectively as they do, and have been waiting for more universal reaction conditions. Two recent papers address these issues. The title of the

To Deprotect and Serve

Several weeks ago I did my annual analysis of the synthetic routes used to prepare small molecule drugs approved by the FDA in the preceding year, obviously in this case 2022.1 I  hope those of you who have seen the presentation found it as interesting to watch as I found to put it together. One

Almost Two Centuries Later, Functional Group Tolerant Conditions Identified for the Electrochemical Kolbe Coupling!

Two principles that we at Scientific Update teach in the foundational “Chemical Development” course are that new experimental methods can open new opportunities for old reactions, and that as scientists we should be looking to understand the mechanisms of empirical observations. Both of these principles are exemplified in by a recent pre-print publication by the

Keeping Count Sometimes Isn’t So Easy

“How many steps are there in a synthetic route?” is one of the foundational questions for any chemist, but as with many apparently simple questions, the answer isn’t always that simple. In many cases chemists are incentivized to give an artificially low step count because it makes their new route look better and therefore more

Triphenylphosphine Oxide- Waste Not, Want Not

Love it or hate it, triphenylphosphine oxide (TPPO, Figure 1) is something we all encounter at some point during our chemistry careers. Most of the time it’s just a by-product from well-established and widely used process such as the Mitsunobou, Wittig, Staudinger, Appel and Corey-Fuchs reactions.1 I remember having a vial full of the white,

A Mild Method for Dehydration of a Base-Sensitive Primary Amide- Toward a Key Intermediate in the Synthesis of Nirmatrelvir

Nirmatrelvir, the active ingredient of the Pfizer drug Paxlovid (Figure 1), is an inhibitor of the SARS-CoV-2 main protease enzyme.1 A key transformation- the final synthetic step in the synthesis of Nirmatrelvir- is dehydration of a primary amide (Figure 2).The amide starting material is prepared by reaction of the corresponding ester with ammonia.2 Various methods

Impurities – How Do You Combat Those Elusive Threats?

Many organic impurities, such as nitrosamines, are known to be harmful to human health. Therefore, regulatory bodies and government set strict limits to protect us all. Even in small quantities, pharmaceutical impurities can have serious negative health impacts and influence the behaviour and efficacy of a drug. Organic impurities fall into a number of categories.

Now You See Me, Now You Don’t- a Judicious Work-Around for Over-Bromination at Benzylic Carbon

One of the most challenging reactions we carry out as synthetic chemists is bromination of a benzylic carbon- the so called Wohl-Ziegler reaction.1 It’s a seemingly simple transformation – not particularly difficult to perform- and potentially very useful. In fact it’s a little too easy. Just add NBS and a radical initiator to an aryl

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