Welcome to the Biotage Flash Purification Blogs.

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

      November 21, 2019 at 3:59 PM / by Bob Bickler posted in Amine, Chromatography, Gradient, Normal phase, Optimization, Polar, Solvents, Troubleshooting, TLC

      4 Comments

      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.

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      Why can’t I reproduce my TLC separation using flash column chromatography?

      November 21, 2019 at 3:48 PM / by Bob Bickler posted in Optimization, TLC

      9 Comments

      You have performed your synthesis and now it is time to purify the reaction mix. You have used thin-layer chromatography (TLC) and see a separation but when you try to purify with flash column chromatography, you can’t get the target compound separated from an impurity. So, what is happening (or isn’t happening)?

      In this post I will give some input on why some separations are not transferable from TLC.

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

      November 21, 2019 at 3:45 PM / by Bob Bickler posted in Gradient, Optimization, Polar, Solvents, TLC

      3 Comments

      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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      How many times can I reuse my flash chromatography column?

      November 21, 2019 at 3:40 PM / by Bob Bickler posted in Gradient, Normal phase, Optimization, Polar, Solvents, Troubleshooting

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      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.

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      Flash column equilibration – is it a waste of time or necessary step?

      November 1, 2019 at 9:30 PM / by Bob Bickler posted in Optimization, Media, Theory

      2 Comments

      slash column chromatography has been practiced by chemists since the 1970s. That practice requires the silica in the column be properly wetted to remove trapped gasses and ensure uniform flow (remember those days of not letting air into the column?). Today, with automated flash chromatography systems and pre-packed columns as the norm, chemists ask me – do I really need to pre-equilibrate my column?

      In this post I explore the impact on chromatography that equilibration, and lack thereof, has on separation performance.

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      How important is your flash column’s plate count, aka efficiency, to your purification?

      October 29, 2019 at 5:00 PM / by Bob Bickler posted in Optimization, Media

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      Plate count is a theoretical number describing the separation efficiency of a chromatography column. In short, it is a measure an eluting compound's bandwidth at the time it elutes from a column, Equation 1.

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      Biotage vs Biotage, and the winner is...

      October 23, 2019 at 9:28 AM / by Panagiotis Ioannidis posted in Chromatography, Optimization

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      When Isolera™ was launched, the maximum system pressure that could be reached was 10 bars, but reaching that pressure was a challenge since most of the Flash columns could not withstand the higher pressures. The maximum pressure rating for the Biotage® SNAP columns, for example, is limited to five or seven bars, depending on the size, and columns from most of manufacturers have the same limitation.

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      Six key factors that impact flash chromatography

      October 18, 2019 at 9:54 PM / by Bob Bickler posted in Optimization, Solvents, Media

      2 Comments

      In this post I will delve into six key factors that impact your purification success in flash column chromatography.

      Previously, I have discussed the use of TLC for solvent scouting and method development and optimization. I have have also talked about cartridge size, particle size, and surface area and their impact on flash purification.  Here I integrate that information into the six factors below.

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      How do I purify my high boiling solvent reaction mixture using silica flash chromatography?

      October 18, 2019 at 9:48 PM / by Bob Bickler posted in Optimization, Solvents

      2 Comments

      Many chemists today find they need to synthesize molecules at higher temperatures in order to force difficult reactions to proceed. Solvents such as DMF, DMSO, and NMP are commonly used in these reactions as they facilitate the use of the high reaction temperatures.  However, the same attributes that make these chemicals attractive as reaction solvents make compound recovery from them very difficult, including flash column chromatography.  These high boiling solvents are typically polar and pose a challenge if purification is to be accomplished with normal-phase silica.

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

      October 4, 2019 at 6:30 PM / by Bob Bickler posted in Cannabis, Chromatography, Gradient, Normal phase, Optimization, SNAP, Solvents, Troubleshooting, Selekt, Media, Mass-directed purification, Theory

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      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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      What is a Chromatography Gradient?

      October 2, 2019 at 3:27 PM / by Bob Bickler posted in Gradient, Optimization

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      Gradients, used in chromatographic methods, assist with chemical separation and elution. They begin with “weak” elution conditions and end with “strong” elution conditions.

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      Using TLC to Scout Flash Chromatography Solvents

      September 20, 2019 at 3:06 PM / by Bob Bickler posted in Optimization, Solvents, TLC, Theory

      3 Comments

      TLC is the tool most used for normal-phase flash chromatography method development. For many chemists, a solvent system of hexane (or heptane) + ethyl acetate is the first, and sometimes only, solvent system evaluated. Though often useful, ethyl acetate may not always provide the optimal purification conditions.

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      How do I Create an Efficient Gradient Flash Chromatography Method?

      September 20, 2019 at 2:58 PM / by Bob Bickler posted in Gradient, Optimization

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      For most organic and medicinal chemists flash chromatography is just another step in the synthesis work flow - react, analyze, purify, react, analyze, purify... until the final product is made. The desired product of each reaction, and the mixture of other species present are, of course, different with each cycle.  Separating the desired compound efficiently without a lot of hassle is something I have written about in this post as well as in others in this series.

      In this post, I've written about how that TLC (thin layer chromatography) plate you use for monitoring your reaction can be used to create reliable, efficient, effective gradients.

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      What is Flash Chromatography and why should I do it?

      August 20, 2019 at 5:34 PM / by Bob Bickler posted in Optimization

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      Flash chromatography is a chemical separation technique used to purify chemical mixtures. Because it is a purification technology, the process is also referred to as flash purification.

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      How to minimize particulate build-up in flash chromatography systems

      July 9, 2019 at 3:23 PM / by Bob Bickler posted in Optimization, Media

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      In order to perform flash chromatography consistently, the equipment you use must be properly maintained by following some “best practices”. These best practices include using clean solvents (I typically use ACS grade), volatile organic modifiers, and quality columns.

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      How changing stationary phase chemistry can impact separation selectivity

      June 12, 2019 at 2:42 AM / by Bob Bickler posted in Optimization, Media

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      Challenging separations, we all have faced this vexing problem. You synthesized your compound, analyzed it, and know your molecule is in there, based on LC-MS or TLC. Then, you do some method development using a silica TLC plate and see a major spot with some minor, early-eluting impurities. You think that the purification will be easy only to find that your “purified” compound has some co-eluting impurities. Now what? Should you change solvents or change stationary phase?

      In this post, I will show how changing the column media but keeping the same solvents removed a co-eluting impurity in one of my reaction mixes.

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