Welcome to the Biotage Flash Purification Blogs.

    5 Steps to successful flash chromatography

    April 20, 2020 at 10:15 AM / by Bob Bickler posted in Amine, Chromatography Fundamentals, Reversed-phase, Solvents, Media and Resin, Loading Techniques, Normal Phase, Pillar Page

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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.

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    Pushing flash column chromatography loading limits

    December 30, 2019 at 3:39 PM / by Bob Bickler posted in Chromatography Fundamentals, Green, Sfär, Loading Techniques, Cost, Normal Phase, Pillar Page

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    A question I hear a lot from chemists is “how much can I load”. The answer is always “it depends on your separation quality”.  At that point I begin asking about the TLC data and purification goals. Purification goal setting should be your first step and the question to answer is – what do I need this purification to achieve? Is the goal high purity, high yield, or some combination.  Remember, you will typically sacrifice purity for high yield and yield for high purity so optimization is an important consideration.

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    Organic Chemistry Workflow – Typical Steps and Equipment

    November 12, 2019 at 3:04 PM / by Bob Bickler posted in Workflow, Sfär, Selekt, Loading Techniques, Normal Phase, V-10, Pillar Page, Initiator

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    Synthetic organic chemistry is the genesis of new pharmaceutical and commercial chemical products. In short, it is based on the idea that two or more carbon-based compounds can be forced to react using heat, or other energy source, to create a new, novel product – but this we already know.

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    How to prevent compound precipitation during flash column chromatography

    November 1, 2019 at 9:34 PM / by Bob Bickler posted in Reversed-phase, Solvents, Troubleshooting and Optimization, Selekt, Loading Techniques, Normal Phase, Isolera

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    Compounds precipitating during flash chromatography is at best an inconvenience when working up your crude reaction mixture.  Precipitation during purification typically happens in the column or in the tubing exiting the column.

    In this post, I will propose a strategy that can minimize and perhaps prevent this issue from occurring.

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    What is the optimal sample to sorbent ratio for dry loading in flash column chromatography?

    November 1, 2019 at 9:32 PM / by Bob Bickler posted in Sfär, Selekt, Media and Resin, Loading Techniques

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    For chemists preferring or needing to dry load their crude sample mixtures to get an acceptable flash purification result, using the right ratio of sample to sorbent can be quite important.  Too much sample and solubility issues can ensue, too little sample and significant band broadening occurs, reducing the separation quality.

    In this post, I propose an acceptable ratio range based on my own experimental data.

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    When should I use dry loading instead of liquid loading with flash column chromatography?

    October 4, 2019 at 6:17 PM / by Bob Bickler posted in Chromatography Fundamentals, Reversed-phase, Synthesis, Workflow, Media and Resin, Loading Techniques

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    Many microwave assisted organic synthesis (MAOS) reactions use polar solvents such as alcohols, DMF, DMSO, because they absorb and transfer microwave energy very efficiently.  However, the downside of using polar, microwave absorbing solvents is that they can interfere with normal-phase flash chromatography.

    In this post, I discuss why dry loading can be advantageous when purifying polar-solvated reaction mixtures.

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    Which injection solvents should I use for reversed-phase flash purification?

    September 20, 2019 at 8:21 PM / by Bob Bickler posted in Chromatography Fundamentals, Reversed-phase, Solvents, Loading Techniques

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    In previous posts I have touched upon various sample loading options and how they impact flash chromatographic performance, primarily in normal-phase flash purification. As the use of reversed-phase flash chromatography has steadily increased over the past few years I thought it would be a good idea to discuss one of the most important factors impacting its success.

    In this post I discuss the results of some of my original research studying the impact of injection solvent choice on reversed-phase flash separations.

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    Preparation and use of an internal dry loading device for flash chromatography

    September 17, 2019 at 2:15 PM / by Bob Bickler posted in Sfär, Loading Techniques, V-10

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    Your choice of sample loading technique can, and likely will, affect the separation and purity of your targeted compound. While liquid loading is easy and often fit for purpose, it can provide some issues especially if large sample volumes are required relative to column size (> 1% of a column volume) or the dissolution solvent is too strong for the chosen purification method (e.g. injecting a methanol-solvated sample into a hexane/ethyl acetate mobile phase).

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    What are good reversed-phase dry load options?

    July 23, 2019 at 2:40 PM / by Bob Bickler posted in Chromatography Fundamentals, Reversed-phase, Sfär, Loading Techniques, HPLC

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    Using a “dry” loading technique with flash chromatography typically improves compound purity and overall separation quality compared to liquid loading. The reasons for this I have prophesized previously and include:

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    Which loading method should I use for purification by flash chromatography?

    July 10, 2019 at 3:14 PM / by Bob Bickler posted in Loading Techniques, Normal Phase, Isolera

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    Getting the most benefit from your crude sample purification with column chromatography or flash chromatography involves optimizing many variables.  In previous posts I have talked about selecting the best solvents, their ratios, and maximizing load based on TLC Rf data. These are all important chromatography-generated variables but now I would like to share some tips on actual technique differences and their impact on purification performance.

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    How do I determine loading capacity in reverse phase flash column chromatography?

    July 10, 2019 at 3:01 PM / by Bob Bickler posted in Chromatography Fundamentals, Reversed-phase, Media and Resin, Loading Techniques

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    As the popularity of prep-scale, reversed-phase flash chromatography increases, so does the frequency that I get asked this question, "How do I determine loading capacity in reversed-phase flash chromatography?"

    In the world of HPLC, loading capacity isn’t normally a concern as it is primarily an analytical technique.  In the synthetic organic chemistry world, most purification is performed with silica gel where flash column purification methods are developed and loading capacity estimated from TLC data.  However, when normal-phase flash does not work and reversed-phase flash is needed, the question of how to determine reversed-phase loading capacity comes up.

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    How much DMF or DMSO can I inject on my reversed-phase flash chromatography column?

    June 13, 2019 at 5:05 PM / by Bob Bickler posted in Chromatography Fundamentals, Reversed-phase, Solvents, Media and Resin, Loading Techniques

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    In a previous post I shared results of experiments where I evaluated selected organic solvents for sample dissolution and injection for reversed-phase flash purification.  I demonstrated that DMF and DMSO both are excellent solvents for this purpose and actually provide better chromatography than methanol, acetonitrile, and acetone.

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    How many ways can you load sample on your column?

    May 31, 2019 at 4:02 PM / by Raffaella Bombarda posted in Chromatography Fundamentals, Green, Sfär, Loading Techniques, Scale-Up

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    Biotage®, a pioneer in Flash Purification, launched the unique, removable cap SNAP flash chromatography columns in 2007. This beneficial column design feature continues with the newest Biotage flash columns named Sfär columns.

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    Dry loading media options – diatomaceous earth

    May 28, 2019 at 10:47 PM / by Bob Bickler posted in Sfär, Media and Resin, Loading Techniques

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    Various flash chromatography sample loading options are available including liquid and dry loading. Choosing the right technique is important because your sample loading choices (sample solvent and dry load sorbent), can have a major impact on the results.

    In this post, I compare the two techniques and show the benefits dry loading with a form of diatomaceous earth can bring to your purification.

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    Webinar: A Roadmap to Successful Chromatography

    March 19, 2019 at 10:00 PM / by Bob Bickler posted in Chromatography Fundamentals, Reversed-phase, Troubleshooting and Optimization, Webinar, Loading Techniques

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    On July 26th, 2018, Bob Bickler, Senior Technical Specialist, recorded a webinar on A Roadmap to Successful Flash Chromatography. To learn more, read the description below as well as watch the recording!

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    Which dry load sorbent should I use for flash column chromatography?

    February 19, 2019 at 10:55 PM / by Bob Bickler posted in Sfär, Selekt, Media and Resin, Loading Techniques

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    This is an interesting question that does not have a straightforward answer. In fact, there are many materials that are potentially useful sorbents for dry loading crude mixtures. Some of the more popular are silica, diatomaceous earth (e.g. ISOLUTE® HM-N, Celite®), alumina, and Florisil®. The sorbent choice can influence your purification results because each of the available media have different chemistry and capacity. In most cases, sample/sorbent reactivity really is not a major concern, though it can occur. What is important is the sorbent’s capacity to adsorb/absorb all of your sample and the ratio of your crude sample to the amount of dry load sorbent.

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