Welcome to the Biotage Flash Purification Blogs.

    Does reagent and reaction solvent order impact product yield and purity?

    October 19, 2021 at 6:00 PM / by Bob Bickler posted in Solvents, Synthesis, reaction, reagent

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    This is a question I asked myself while I have been studying synthesis variables to see what, if any, impact each variable has on reaction product yield and purity. For this post, I evaluated the order in which I added reactants and solvent.

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    Can maximizing product yield and purity from messy reaction mixture be green?

    October 5, 2021 at 8:42 PM / by Bob Bickler posted in Green, purification, reaction, orthogonal

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    Chemical reactions gone wrong, I’m sure we all have experienced this issue, I know I have. You add your reagents in the proper amounts with a suitable solvent and perform your reaction only to find your by-product yield was greater than your product; by a lot. So, what do you do to isolate what little product you created with maximum yield and purity without breaking the proverbial bank on a big flash column and the solvent required for the purification?

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    Can water be used as an organic synthesis solvent?

    September 23, 2021 at 2:28 PM / by Bob Bickler posted in Synthesis, purity, water

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    What is Orthogonal Flash Chromatography and Why Should I do it?

    September 7, 2021 at 3:15 PM / by Bob Bickler posted in Reversed-phase, Normal Phase, orthogonal

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    Think of orthogonal flash chromatography as 2D-chromatography where a reaction mixture or natural product extract is purified first with one methodology or solvent gradient then re-purified with a different method or solvent pair in order to remove co-eluting impurities. This is a technique practiced in medicinal chemistry, especially for final compound purification, when the final product is purified first with normal-phase flash followed by reversed-phase prep HPLC.


    There are two general flash chromatography techniques...

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    What are alternatives to DCM/MeOH for polar reaction mix purifications?

    August 24, 2021 at 6:00 PM / by Bob Bickler posted in Solvents, Green, purification

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    For most chemists purifying organic reaction mixtures, normal-phase flash chromatography is the go-to technique. Why not, it is quick, relatively efficient, and can provide relatively high loading capacities if the separation is properly optimized. However, most of these same chemists rely on only two sets of solvents to perform these purifications…

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    How does an acid pH affect reversed-phase chromatography separations?

    August 10, 2021 at 6:00 PM / by Bob Bickler posted in Reversed-phase, acid, pH

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    Chromatography is as much an art as it is a science. Between synthetic reaction products and natural products, the range of compounds requiring separation, purification, and isolation is broad and diverse creating challenges from time to time. Because of this diversity, not all chromatographic separations can be performed with a “neutral” solvent system – one without added pH modifiers or buffers.

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    Does Detection Wavelength Influence Compound Purity and Recovery?

    June 29, 2021 at 7:09 PM / by Bob Bickler posted in purification, wavelength

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    Automated flash chromatography systems have helped synthetic chemists speed up their synthetic research. One major advancement with these systems over the past 15 or so years has been the addition of photo-diode array ultraviolet (PDA-UV) UV detectors with which chemists can detect and fractionate using one, two, or multiple wavelengths. Enabling detection and fractionation with multiple wavelengths increases the likelihood that target and by-product compounds will be isolated with increased purity.

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    Does dry load media choice impact reversed-phase flash purification results?

    June 15, 2021 at 4:07 PM / by Bob Bickler posted in Reversed-phase, dry load, media

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    Flash chromatography is a purification technique used by chemists to isolate their targeted compound from by-products and impurities. Because the reaction mixture (or natural product extract) may have its best solubility in a solvent that is chromatographically “stronger” than the mobile phase, liquid sample loading can be problematic causing early eluting and/or broad peaks with poor purity. In those cases, a technique called dry loading is frequently used.

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    Can dry load media choice impact normal-phase flash purification quality?

    June 2, 2021 at 4:28 PM / by Bob Bickler posted in Normal Phase, dry load, flash chromatography

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    Flash chromatography is a purification technique used by chemists to isolate their targeted compound from by-products and impurities. Because the reaction mixture (or natural product extract) may have its best solubility in a solvent that is chromatographically “stronger” than the mobile phase, liquid sample loading can be problematic causing early-eluting, broad peaks which can reduce purification efficacy and product purity. In those cases, a technique called dry loading is a better alternative.

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    What is the maximum volume I can load on my reversed-phase flash column?

    May 19, 2021 at 2:11 PM / by Bob Bickler posted in Reversed-phase, Solvents, loading capacity

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    With all forms of chromatography there are limitations relating to sample load – both mass and volume. These are independent variables which, for the best results, should be investigated separately. In this post, I will address the impact of increasing solvent volume on flash chromatographic separations.

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    What is my C18 flash column's loading capacity?

    May 5, 2021 at 2:27 PM / by Bob Bickler posted in Reversed-phase, loading capacity

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    A good question I get asked frequently to which there is no specific value. When asked this question I answer, “it depends on your sample and how good your separation is”; not a satisfying response, but it is the truth.

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    Does flash column equilibration volume impact purification results?

    April 20, 2021 at 3:21 PM / by Bob Bickler posted in Chromatography Fundamentals, Solvents, Sfär, Selekt, purification, equilibration

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    Chemists using silica columns for normal-phase flash chromatography typically equilibrate their columns prior to loading their samples. Companies manufacturing automated flash purification systems often have the equilibration volume and flow rate pre-programmed and tied to a column size. Some of these flash system companies allow equilibration volume to be edited while others have the volume fixed.  Is one of these options better than the others? In this post I discuss how equilibration volume impacts flash chromatography results.

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    How can I dry my temperature-sensitive product without degradation?

    April 7, 2021 at 1:44 PM / by Bob Bickler posted in solvent evaporation, degradation

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    Have you ever been faced with the challenge of evaporating solvent from a reaction mixture where the target compound and perhaps some by-products are temperature sensitive and degrade or decompose with elevated heat? How do you efficiently accomplish this evaporation challenge?

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    What is the best way to purify a crude reaction mixture that auto-crystallizes?

    March 23, 2021 at 4:55 PM / by Bob Bickler posted in purification, crystallization

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    For chemists isolating their synthesized product in maximum yield and purity is a primary goal. Sometimes the crude reaction mixture stays in solution, sometimes it does not. In these cases, is it better to just redissolve in a strong solvent, say DMSO, or to filter, wash, and then purify? After all, the precipitating material may be unreacted starting material and could potentially complicate the subsequent flash purification step. On the other hand, it may be product crystallizing on its own and worthy of your attempt to isolate it without further work-up other than filtration.

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    How to Purify your Target Compound with Minimal Impurities

    February 23, 2021 at 2:05 PM / by Bob Bickler posted in Chromatography Fundamentals, purification

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    Purifying your synthetic product efficiently in high yield with minimal impurities is every chemist’s goal. At discovery-scale, flash chromatography is the go-to purification technique as it is relatively simple and effective.

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    How does gradient slope impact flash chromatography loading capacity?

    February 9, 2021 at 1:40 PM / by Bob Bickler posted in Chromatography Fundamentals, Reversed-phase, Troubleshooting and Optimization, Scale-Up

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    For many synthetic chemists the primary purification goal is to isolate as much synthetic product as possible with a minimum of 80% purity. The go-to technique for product isolation is flash purification (flash chromatography), especially for intermediates.

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