Not all Pans are Created Equally Safe

When it comes to thermal hazard assessment, differential scanning calorimetry (DSC) takes a special place in the landscape of possible testing methods. Both for rapid screening of a wide variety of samples, and for the gathering of the necessary high-quality data for a detailed kinetic study of decomposition reactions, DSC is usually the instrument of

Using QbD and DoE for the Systematic Optimisation of a Telescoped Process

In this paper (Gonzalez et al., Org. Process Res. Dev. 2019, 23, 6, 1143-1151) from the Chemical and Synthetic Development team at Bristol-Myers Squibb, DoE and QbD methodologies have been used to develop a telescoped process for the API step in the route to a reversible inhibitor of BTK. (Scheme 1) Scheme 1: Two step

Can the Formation of N-Nitrosamines in Formulated Products be Inhibited?

Over the last year we have seen a substantive shift in terms of the type / nature of N-Nitrosamines we have seen, moving from the process related small simple dialkyl N-Nitrosamines seen in Valsartan, such as NDMA / NDEA, to API like N-Nitrosamines.  Our knowledge is such that we now have a good understanding of

Keeping it Clean

Multipurpose facilities for batch processing remain ubiquitous in the process industries for relatively short campaigns of diverse products.  Whether the products be active pharmaceutical ingredients, foods, agrochemicals, or other fine and specialty chemicals, those producing them face a  shared problem: how to satisfactorily remove residues of the previous campaign from the plant before commencing on

A Good Whipping | How ‘pencil-whipping’ check-lists could have serious consequences

I was recently standing with several colleagues on the mezzanine level of a small batch manufacturing plant watching an operator charge LiOH-H2O into a reactor manway. Without warning we were all suddenly hit with a punch to the throat from inhalation of invisible caustic dust that had aerosolized during the charging, and we were forced

Grease is the word…

Many years ago, I heard an anecdote regarding a fortuitous discovery in the Sharpless lab. A graduate student had been awarded their PhD and the group were celebrating in the lab with bottles of red wine (I know- but they were different times). Someone in the group-who had obviously consumed a sufficient quantity of the

Electroorganic Synthesis Using Alternating Current

During the past few years the application of electrochemical methods for organic synthesis attracted increasing attention both in academia and industry.1 Electroorganic synthesis rely on interaction of the starting materials with electrodes in an electrochemical cell to realize redox chemistry. As inert an inexpensive substances, such as water, can be used as electron donor and

A Scalable Birch Reduction

The Birch reduction is a great reaction on small scale and can be carried out on large scale but requires specialist equipment to handle liquid ammonia (bpt -33°C) and it takes a significant amount of time to evaporate the ammonia at the end of the reaction. There have been various reports of alternative methods using

Live at the palladium

In March 1989, two chemists, Stanley Pons and Martin Fleishmann, stunned the world by claiming that an electrical current from a palladium electrode immersed in a test tube of water had resulted in nuclear ‘cold fusion’ at room temperature.1 For many years, attempts to understand and reproduce this seemingly impossible result- with sketchy information from

Temozolomide- Mr kiss kiss bang bang

It’s not often that drug molecules find themselves on the reagent shelf alongside materials that may have been used to assemble them. The prince and the pauper so to speak. In 2019 Paul Hergenrother from the University of Illinois published a paper in Angewandte Chemie claiming a diazomethane surrogate that was a commercially available, weighable, solid:

Veni Vidi Vici (I came, I saw, I conquered)

A couple of interesting papers published recently on aryl iodination. I sure I don’t need to reiterate how useful iodinated intermediates are in synthesis- most significantly their heightened reactivity in metal catalysed cross coupling chemistry,1 and, more recently their application as organocatalysts in hypervalent iodine chemistry.2 As is common in synthetic science, the intermediates you

Fluorinate to accumulate- simple methods paying rich dividends

In June of 1886 (26th to be precise) the French chemist Henri Mossian passed an electric current through a solution of KHF2 in anhydrous HF and became the first person to generate fluorine. Rather him than me. But he did, quite rightly, win a Nobel prize for his efforts in 1905. Since then, methods to

Discovery and Development of Novel Enzymes

I recall back in the late 1980’s, working for Smith Kline and French, reading a couple of articles in Tet. Letts. on biotransformations. I was intrigued, and a bit sceptical, that such transformations with enzymes would take place and lead to efficient large-scale processes. I had no experience or training in this area. My degree

It’s Not Goodbye but Au Revoir !

In March 2022, Dr Will Watson will be hanging up his laser pointer and commencing on new adventures as he starts his well earned retirement. Will has been a hugely valued member of the Scientific Update team since he joined in May 2000. During his 21+ years at the company he has trained more than