For medicinal chemists, maximizing the synthetic yield of their newly created intermediate compound is their priority. More times than not, flash chromatography is used to purify these intermediate compounds to at least 80% purity. Final compounds, however, not only require high yield but maximum attainable purity, typically in excess of 95%. For this purity level, chemists will either send the reaction mixture to an in-house prep HPLC lab or perform their own preparative HPLC compound purification, if it is available in the lab.

Choosing a good purification strategy is an important for successful crude compound purification. A major factor in your strategy is choosing between normal-phase or reversed-phase chromatography.  How do you choose?

In this post, I will provide some simple guidance on helping determine which route to take.

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.

Over the past several decades, the chemical industry has implemented process changes and updated practices in R&D and manufacturing in an effort to reduce liquid and solid lab waste. The pharmaceutical industry in particular has taken steps within their drug discovery labs to reduce solvent use by requiring their chemists to find and implement measures that achieve the corporate environmental goals without curtailing their productivity – quite the challenge.

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.

This, of course, is always one of the first questions an organic, medicinal, or peptide chemist has when starting the research process for a flash chromatography system. Here at Biotage, we receive this question hundreds and hundreds of times a year, likely within the first couple of minutes of any conversation.

Up to six compounds can be easily separated with an automated step-gradient optimizer embedded in modern flash chromatography systems.

The newly released Biotage® Selekt flash chromatography instrument can be run at a maximum flow-rate of 300 mL/min or a maximum pressure of 30 bar. These high flowrates and pressures enable a user to perform chromatography using not only dry-packed, single-use plastic flash columns containing small (≥20 μm) spherical silica particles, but also semi-preparative, slurry-packed
HPLC columns for multiple use with smaller (≤20 μm) spherical silica particles.

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

In all my years of working with medicinal and organic chemists, I have found that choosing how many grams of silica to use for purification by flash chromatography is something frequently guessed at. Getting the size of the column right is awfully important because using too few grams of silica will doom your purification to failure and using more an optimal mass of the stationary phase means the purification consumes excess silica, solvents, and a chemist's time.

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.

This is a question being asked of my colleagues and me more and more frequently, especially in pharma accounts.  Why?  Well, you are familiar with the adage – Time is Money, right.  Well this really applies to them. A new molecular entity (NME) created as a pharmaceutical can take up to a decade and a billion dollars to bring to market.  Granted, the biggest costs are in the clinical trials but the synthetic route and the time to discover and make the compound – and purify it – plays a major role within drug discovery and development. This timeline is not helped by the ever increasingly difficult-to-synthesize compounds being investigated as drug candidates today.

With that in mind, this post focuses on ways to speed the purification process without sacrificing purity and yield.

In our more environmentally aware climate, chemical and pharmaceutical companies now prioritize reducing organic solvent use in chemistry labs. Employees and shareholders alike are pushing their companies to become greener which impacts how chemistry, both synthesis and purification, is performed.

Varying the concentrations of mobile phase solvents during  flash purification chromatography enhances the ability of the technique to effectively isolate the desired compound from reaction by-products and unconsumed reagents.  Choosing how these concentrations will be varied over time has a significant effect on the purity and recovery of desired compounds.

Reversed-phase flash chromatography usage is increasing rapidly. In fact, over the past 10 or so years, reversed-phase flash chromatography use has increased a dramatic 650%! This is amazing growth despite the fact that reversed-phase flash columns are considerably more expensive than silica columns and you need to evaporate water from your fractions. So, what’s driving this change in chemists’ modus operandi?

In this post, I will explain why chemists are increasingly using reversed-phase flash chromatography for routine, intermediate, and final compound purification and provide and example as well.

Most flash column manufacturers now offer “high performance” flash chromatography columns with the promise of higher loading, increased purity, and even reduced solvent consumption. Working for Biotage, I have made those valid claims for our products as well.