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Sodium Azide-Sonic Boom Boy

Last week I was in Madrid running our chemical development and scale up course. I met a great group of people, one of whom worked at Dynamit Nobel. During a coffee break we struck up a conversation about (of all things) azides, in particular sodium azide. Fairly quickly we both discovered that we had no

To Deprotect and Serve

Several weeks ago I did my annual analysis of the synthetic routes used to prepare small molecule drugs approved by the FDA in the preceding year, obviously in this case 2022.1 I  hope those of you who have seen the presentation found it as interesting to watch as I found to put it together. One

Triphenylphosphine Oxide- Waste Not, Want Not

Love it or hate it, triphenylphosphine oxide (TPPO, Figure 1) is something we all encounter at some point during our chemistry careers. Most of the time it’s just a by-product from well-established and widely used process such as the Mitsunobou, Wittig, Staudinger, Appel and Corey-Fuchs reactions.1 I remember having a vial full of the white,

A Mild Method for Dehydration of a Base-Sensitive Primary Amide- Toward a Key Intermediate in the Synthesis of Nirmatrelvir

Nirmatrelvir, the active ingredient of the Pfizer drug Paxlovid (Figure 1), is an inhibitor of the SARS-CoV-2 main protease enzyme.1 A key transformation- the final synthetic step in the synthesis of Nirmatrelvir- is dehydration of a primary amide (Figure 2).The amide starting material is prepared by reaction of the corresponding ester with ammonia.2 Various methods

Now You See Me, Now You Don’t- a Judicious Work-Around for Over-Bromination at Benzylic Carbon

One of the most challenging reactions we carry out as synthetic chemists is bromination of a benzylic carbon- the so called Wohl-Ziegler reaction.1 It’s a seemingly simple transformation – not particularly difficult to perform- and potentially very useful. In fact it’s a little too easy. Just add NBS and a radical initiator to an aryl

Light, Camera, Action- Photoinduced Oxygen Transfer using Nitroarenes to Cleave Alkenes

When one thinks about the chemistry of alkenes, oxidative cleavage via ozonolysis will be close to the top of the list. Certainly in the top 5. Discovered by the Swiss chemist Friedrich Schönbein in 1839, this reaction remains -both academically and industrially- a highly efficient, sustainable method for introducing oxygen into both simple feedstock materials

PerFected Cubane

In the spring of 1940, John Archibald Wheeler, eminent theoretical physicist, called up his then PhD student, Richard Feynman (generally regarded as the most famous modern-age physicist) and said “Feynman- perhaps there’s only one electron in the Universe” a single entity moving backwards and forwards in time. If true it would be one hard working

Something Unique or Methyl, Butyl, Futile? Born again Boron

I can’t begin to count the number of aryl boronic acids I’ve made and/or worked with over the years. These versatile intermediates will forever be part of the synthetic organic chemist’s toolbox. You would be hard pushed to find an organic chemist that hasn’t run a Suzuki- Miyaura cross coupling reaction at some stage in

Rhodium takes Frigid Phenol to New Heights

Phenols and anilines are two of the most important building blocks in industrial chemical manufacturing. Any process capable of converting one into the other is going to generate a lot of interest, and a paper by Shi and co-workers does just that.1 Direct conversion of an aniline to a phenol is a relatively straightforward transformation

Metal Hydride? NO Protection, NO Problem and NO-Where to Hide

Process chemists at Genentech recently published their work on development of a kilo-scale synthesis of JAK-1 inhibitor- GDC-4379 (Figure 1).1The central heterocyclic core of the molecule consists of a 4-aminopyrazole moiety (elaborated as the pyrazolopyrimidene amide- presumably the inhibitor hinge binding fragment in the kinase active site) with an additional aryl substituent at C-3 and

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