5 Steps to successful flash chromatography

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.

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How does solvent choice impact reversed-phase flash chromatography separations?

I have recently posted on how solvent choice influences the separation of hard to resolve compounds using normal-phase flash chromatography. As a chemist with an inquiring mind, I thought I would expand my research beyond normal-phase and see what happens in reversed-phase.

In this post, I share my results. 

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How many times can I reuse my flash chromatography column?

Flash chromatography – a purification tool for both organic chemists and natural product researchers.  This tool is essential when you need to remove impurities from your targeted product, or products, in order to get them pure.  To reduce the costs associated with flash chromatography, some chemists try reusing the same column over and over, not always with success.

A question I am frequently asked is “how many times can I reuse my flash column?” Although I have previously addressed this topic, I feel it is worth another look. In this post, I will attempt to address this question by providing a bit more science behind the cartridge reuse question.

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Ionizable compound purification using reversed-phase flash column chromatography

With most chromatographic purifications, only two solvents are needed to adequately separate compounds from each other. Unfortunately, there are instances where the separation is either poor or cannot be accomplished with “normal” elution conditions such as those with ionic or very polar organic molecules.

In this post I offer some solutions to this issue.

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How do I purify ionizable organic amine compounds using flash column chromatography?

For most organic reaction mixture purifications the process is fairly straightforward. Use hexane/ethyl acetate or, for polar compounds, DCM/MeOH.  But what do you do if this doesn’t work and your compounds are basic organic amines?

In this post, I re-examine the options available to achieve an acceptable organic amine purification when typical separation methods are insufficient. Continue reading How do I purify ionizable organic amine compounds using flash column chromatography?

How does mobile phase organic solvent choice impact reversed-phase flash column chromatography?

Organic and medicinal chemists frequently utilize flash chromatography to purify their reaction mixtures. Normal-phase flash chromatography is most often used but may not the best methodology, especially when the compounds are quite polar and/or ionizable.

For these molecules, reversed-phase flash chromatography is preferred but often is not used due to an uncertainty regarding the best solvent choices and the reversed-phase mechanism.  In this post, I will discuss how organic solvent choice in reversed-phase chromatography can influence the chromatographic separation.

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Using pH to optimize reversed-phase flash chromatography separations

I have previously posted on the topic of normal-phase optimization by evaluating different solvent blends or mixtures. I have also touched on reversed-phase method development as well suggesting chemists use HPLC to optimize their purification.

In this post, I will look at the impact modifying mobile phase pH can have on reversed-phase separations.

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How do I remove an annoying MS TIC background?

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.

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Cannabis extract purification using orthogonal flash column chromatography

For some cannabis-based product developers reversed-phase chromatography has become the analytical tool of choice for determining the extract content profile as well as for purification of specific cannabinoid compounds. However, the extracts often contain many other compounds which reduce load capacity and purity of the product(s) of interest and then require even more extensive clean-up.

In this post I show the results of an orthogonal flash purification approach that first uses normal-phase flash column chromatography to clean up the crude cannabis extract followed by reversed-phase C18 flash chromatography of the isolated target compounds.  This orthogonal approach to purification increases the targeted product’s purity.

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