Scaling up reversed-phase flash chromatography methods is often necessary as reaction scale increases. This is especially true when other non-chromatographic purification techniques do not work or meet purity and/or yield needs.

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The bane of organic synthesis for most chemists is purification rather than synthesis. Synthetic reaction mixtures are rarely devoid of impurities so some type of purification is necessary.  Most often flash chromatography is used but for many chemists, it is less well understood than their chemical reaction and provides some level of anxiety.

In this post, I will summarize the five most important steps to creating a successful flash chromatography method and thus the anxiety associated with it.

This is an interesting question that I am asked from time to time. There does seem to be two camps in which chemists reside – one believing longer and thinner columns provide better separations and the other preferring shorter and fatter columns to do the same chromatography.

Which is right? That is a question I will try to answer based on my own data.

The Biotage® Selekt Flash purification system is designed for the rapid and simple isolation of target molecules from complex mixtures. Typically, this is seen in the area of drug discovery, where large numbers of molecules are synthesized in order to find active pharmaceutical ingredients for future pharmaceutical use. However, flash purifications can be employed in any work that involves the requirement to purify compounds, which is most branches of chemistry.

Recently, I posted an article explaining why high performance TLC plates are not needed for method development for high-performance flash chromatography.  Based on some excellent feedback, I see a need to discuss silica chemistry and its impact on chromatography.

For many chemists using generic linear gradients and even gradients based on TLC the purification results often are not selective enough to separate all of the compounds in their mix.  This is especially true if your target has a closely eluting impurity. One method used to try and increase resolution is the use of an isocratic hold or gradient pause during purification.

In this post I examine the use of the isocratic hold to determine how well it works and when/if it should be inserted into a gradient method.

Have you ever run flash column chromatography with mass detection (Flash-MS) and observed the total ion current or TIC increase during the purification only to find that there was no discernible compound contributing to the effect?

In this post I discuss how I came across this issue and the solution I found to work.

Chromatography is a common tool of the chemistry laboratory, and most chemists involved in synthesis have a good idea how automated flash purification system work on the lab bench. However, knowing how to take purifications from the laboratory to a manufacturing environment is a different question altogether.

The products of organic synthesis are designed with specific functional groups in order to possess desired properties. Depending on the compound’s functionality, it can be neutral, acidic, or basic as determined by a compound measurement called pKa or acid dissociation constant. Compounds with low pKa are typically acidic while those with high pKa tend to be basic. Compounds with a pKa near 7 are deemed neutral.