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

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

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

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

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

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

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

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

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:

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