The Lab Notes

A recent survey suggested that out of all CMC topics the one at the forefront of many people’s minds and concerns is that of impurity control.  Why might that be the case? After all there is a strong framework provided by ICH in the form of ICH Q3A / Q3B (Impurities in drug substance and…

One of the disadvantages of Miyaura borylation is that normally a diboron ester, such as bis(pinacolato)diboron, needs to be used and the resultant coupled ester has to be hydrolysed to its corresponding acid. This leads to poor atom efficiency and longer processing times. Separating the pinacol waste from desired products can sometimes be challenging. A…

This perspective article, from workers at Imperial College London and Pfizer, Cambridge, reviews the literature on site-selectivity in S-M coupling reactions for a wide variety of heterocycles on a case-by-case basis. It is shown that experimental parameters can critically impact the dominant catalytic species in solution and its ability to undergo the site-selectivity determining oxidative…

The Suzuki-Miyaura cross coupling reaction has been widely used in industry for C-C bond formation but has not successfully been applied to unactivated substrates such as amides and esters, in which the C-N and C-O bonds are cleaved. This recent report from scientists in Wroclaw (Poland), Beijing and New Jersey gets around the normally slow…

Photochemistry is an attractive synthetic method but has not been used widely in industry, except for one or two special processes. In batch processes, the efficiency of light usage is poor, partly owing to the reactors becoming fouled up in the region of the lamp and continuous processes should have more favourable characteristics. There has…

The topic of green and sustainable solvents is of growing interest to industry, which recognizes the need to reduce solvent usage and to minimize the use of certain solvents of toxicological concern. This up-to-date review from the group of Hallett in the Chemical Engineering Dept at Imperial College, London has almost 500 references focusing on…

The concept of borrowing hydrogen (also known as Hydrogen auto-transfer) is a useful concept which combines transfer hydrogenation with other reactions to produce more complex molecules, exemplified by the alkylation of amines with alcohols and the reaction of benzyl alcohol with acetophenone to give 1,3 diphenylpropanone.   For the process chemist these processes seem to be…

ICH M7 provides greater flexibility to assess the risk posed by Mutagenic Impurities.  This is described in section 8 – Control of the guideline and defined as a series of control options.  Of these Option 4 permits an applicant to present an argument for control based on the physico-chemical properties of a mutagen and the…

As someone who did his PhD on photochemistry, I have always been surprised at how little photochemistry is used in making new molecules, given the unusual transformations that photochemistry can enable. However, there has been a resurgence in the use of photochemistry in the last decade in academic laboratories. But the equipment had hardly changed…

The Scale Up of Chemical Processes Conference, June 21st - 23rd 2017 took place in Rochester, NY. For a review of the event by sponsors Kodak Speciality Chemicals - Click HERE