Chemists working in a pilot plant often face safety issues during scale-up operations. With the help of emerging microfluidic applications and microdevices, running hazardous, highly exothermic or potentially unstable reactions can be easily transposed into a safe continuous flow mode. This paper describes how a potentially hazardous pyrazole nitration and the bromination of a variety of electron-rich heteroaromatic substrates were efficiently performed using a cheap and easily available system for bench chemists. Advantages of the continuous flow mode in organic synthetic chemistry will be exemplified by the large-scale production of raw materials under safe, green and reproducible conditions.

The partnership between rational synthesis design and mass-triggered preparative LCMS is a powerful one, capable of furnishing very large libraries in a selective manner in a very short space of time. Herein, we communicate one example of possibly a perfect marriage between the synthetic chemistry and the subsequent purification method employed, affording a ∼1000-member library supplying 50 mg on average of final compound in less than a month.

Preparative RP-LCMS is widely used to purify compounds from crude reaction mixtures in drug discovery today. Method development for preparative Liquid Chromatography-Mass Spectrometry (LCMS) consists of finding the right balance between speed and quality, often leading to the use of fast generic gradients (5-95% organic mobile phase) to purify compounds of various structures and polarity, which can be sometimes detrimental to the purity of the isolated compound. Isocratic elution is the best method to obtain high purity, but it usually requires a long trial and error method development to find the right eluent composition. Therefore it is mostly used to purify large quantities of product using for instance stack injections, but not for routine purification of structurally diverse compounds. Herein, we describe an empirical method that allows "right-first-time" purifications with isocratic elution on preparative RP-LCMS, permitting isolation of compounds in high purity and yield.