Org Prep Daily

March 5, 2016


Filed under: industry life — milkshake @ 5:35 pm


There is a darkly funny story behind this post

I guess you have seen this one before: “Experienced MS level chemist with a track record of research accomplishment is looking for a process development or biopolymer chemistry or medicinal chemistry position in the industry…”


  1. Milkshake…how can I help?

    Comment by seearroh — March 5, 2016 @ 10:25 pm

  2. I am also happy to help.

    Comment by Chemjobber — March 6, 2016 @ 8:19 pm

  3. If this means what I think it means then as an avid reader I wish you all the best.

    Comment by Daniel — March 7, 2016 @ 8:45 am

    • When I get a new job, at a larger company, I don’t know how long I will be able to continue – we will see. Thank you for reading this stuff!

      Comment by milkshake — March 7, 2016 @ 10:10 am

  4. I pray nightly to the chem gods that you will both find lasting and rewarding employment and continue this blog for many years to come!

    Comment by Ian D. — March 8, 2016 @ 4:06 pm

  5. Get your substitute teaching permit process started now. Unemployment runs out fast.

    Comment by jc — March 16, 2016 @ 7:48 pm

  6. Find your dream job yet?
    One of my peeps is hiring,
    send your resume plz.

    Comment by kinasepro — March 26, 2016 @ 12:28 am

    • I haven’t find it yet – I am sending you my resume right away. Thank you!

      Comment by milkshake — March 26, 2016 @ 11:03 am

      • Good luck, Milkshake.

        Have you considered a garage CRO company and hiring some MS students on OPT….I am looking for a job and I am seriously considering…now that outsourcing is so common and you just open a website and offer all the chemicals you can possibly make and make them only when some one places the orders….

        So, I thought of cheeking with you on couple of things….

        1. Should I have town permit to put couple of fumehoods in my garage, a refrigerator and flammable cabinet ( no neighbors to complain as my house is in woods)?

        2. If so, what kind of fumehoods are cheaper and efficient?

        I heard of basement chemistry labs and never heard of garage chemistry labs though I heard of a few garage bio-tech companies. Even if I get employed, probably I could use one such lab to work from home off hrs. What is your take? I am going to leave a fake email and name as I do not want to get into troubles!

        Comment by unemployed — April 7, 2016 @ 7:37 pm

        • I would strongly advise against it, setting up a lab in your house (in woods) will only earn you raid by drug enforcement. Also you will have problem analyzing your products (because you don’t have NMR in your garage). I know a former university professor who set up CRO on his large farm in Ohio – soon he had trouble with waste disposal (he had open vats of organic +salts waste sludge evaporating in a barn…) He could not make living, he pissed off his collaborators and his customers.

          US is not the best country for a CRO – it is hard to compete with fly-by-night cheap CROs around Shanghai, and with well-established all inclusive CROs in US, Canada and Western Europe. The problem is not to make something, the problem is to find a customer who wants to buy it, can make order worth ten thousand USD, and pays in timely fashion.

          If you want to go into manufacturing, chose something outside the traditional organic chemistry/medchem field. Also try to take advantage university incubators – often they have fume hoods installed already, NMR on site and waste disposal service.

          Comment by milkshake — April 7, 2016 @ 10:58 pm

          • Thanks. I am also a bit skeptic about the prospects of such a venture. You guessed it right about the Shanghaian approach. I am taking shelter at a small university campus as of now as a volunteer on post OPT after my PhD and would explore the university incubator option. Nope…I do not know much outside organic synthesis which makes it difficult to diverge.

            Comment by unemployed — April 11, 2016 @ 4:22 pm

          • why don’t you try something with much lower capital entry barrier that you can sell directly? Things like vaping nicotine liquids, swimming pool supplies, artisan soap bars, artisan chocolate? (With soap and chocolate, you can just buy a quality stuff in bulk from abroad, re-melt it, add a little drop of something, cast it and re-sell in small elegant hand-wrapped bars at ridiculous markup to rich fools in fancy mall shops.

            Comment by milkshake — April 11, 2016 @ 5:15 pm

  7. Yes, I am also thinking to move off a bit. I was curious as to what was your comment on Phorbol synthesis @ Baran Group’s blog….I was surprised to see that they were removed!

    Comment by unemployed — April 14, 2016 @ 7:24 am

    • I removed them myself because of triple posting (my internet connection/browser was acting up)

      Comment by milkshake — April 14, 2016 @ 7:36 am

  8. Any news on the job front?

    Comment by wm — March 5, 2017 @ 3:05 pm

    • still looking (had to stay in Prague for awhile, because of dad) – do you know of anything good?

      Comment by milkshake — March 5, 2017 @ 9:57 pm

      • I reckon you are not interested in moving to Europe for a one year medchem position (BSc) at a pharma company?

        Comment by OP — March 14, 2017 @ 2:13 am

        • it really depends on the position. Please send me more information, my e-mail address is in the comment above.

          Comment by milkshake — March 14, 2017 @ 8:02 pm

  9. Hi Milkshake,
    Are you still running your blog since last year, ,sadly, I suppose you didn’t find a new job since there’s no update (or maybe you’re too busy working on new projects?). While never leaving comments through the years, I went many times on your site to read interesting procedures, learn valuable lab tricks and stories about organic chemistry. Thanks for all that. I was hesitant to try to contact you but : do you have any extensive experience regarding difficult heterocycles metallation/anionic chemistry (at least it seems you know quite well that area)? I’m trying to make compounds that are not described in the litterature and I wonder if there is a good reason to this or if I’m just a terrible chemist!

    Comment by N_I — July 25, 2017 @ 4:34 pm

    • Hi, thank you for kind comment. The big name in metallation of heterocycles was Manfred Schlosser, his procedures for metallating pyridines and other elecron-deficient heterocycles are excellent, I reproduced some of them, and they worked on first try (though it was my Scripps colleague Par who did most of the work on this project). Another name worth checking out is Paul Knochel.

      As you know, there are many reasons why direct metallation may fail, often it has to do with functional group incompatibility, organolithium instability, or just solubility issues. I would have to see the exact structure of your substrates. Lack of good close precedents in the literature is always a warning sign.

      Comment by milkshake — July 25, 2017 @ 4:52 pm

      • Thanks for your answer! Indeed, I took quite some time to read the litterature, especially papers from the Knochel group, but the main problem is that I’m working in a university which is not exactly state-of-art in term of equipment and I am a bit afraid of doing this kind of fancy organometallic base synthesis (I only have a vacuum pump and a 120°C oven for glassware drying, no schlenk line, Young flask or anything like that…). I am also limited to test reactions on a 50-100 mg scale making it even harder to be sure it work like it should. I did run experiments with commercial Knochel-Hauser base and TurboGrignard (deprotonate then quench with an heterocyclic aldehyde) but without success.

        I don’t want to bother you with the detail of my lab problems, but If you are interested in seeing what I need to make, maybe I could send you a couple of structures by email (I guess you have access to my adress in the comments)? These are mainly 2,5-diacyl-5 membered heterocycles substituted with other heteroaryls but I can’t really go into details here as it is done for a medchem project. I feel like, more than litterature or procedures, I need feedback and ideas from people who have been doing that kind of chemistry, because there’s no one doing this where I’m working (apart for the classical nBuLi/LDA reaction on easy substrates).

        Comment by N_I — July 26, 2017 @ 7:56 am

        • I don’t think aryl ketones will be compatible with strong base -promoted metalation, the carbonyls will interfere – perhaps that is the reason you cannot find any precedent. I would look for ruthenium-catalyzed carbonyl ortho-directed aryl CH activation instead

          Comment by milkshake — July 26, 2017 @ 8:11 am

          • I started with unprotected ketones since it was done in our lab on another related compound (though they did BuLi metal-iodine exchange on an acylimidazole, not direct deprotonation). The yields for aldehyde addition were around 50-60%. I also tried on OTBS protected substrate but it doesn’t seem to do any better (see to view the compounds I did most reactions on). I would like to find an easier way to make these molecules (thanks for the suggestion of C-H activation but I don’t have any directing group close to the 2 position). I’m sure a Pd carbonylative cross coupling on bromothiophene derivative and boronate esters should work with some optimization but I can’t use CO where I work and using organic precursors is much less effective (I ran a reaction with HCO2H/Ac2O as the CO donor but got only the Ar-Ar coupling product).
            Btw, one last question : do you ever had problems with the quality of your THF for these reactions? I did both Na ketyl distillations or using SPS solvent (dried on alumina column) but from time to time there seem to be some low boiling organic contaminants depending on the batch/bottle/manufacturer. I’m convinced that the reactions I ran with long metallation time are plagued with this issue besides the low reactivity of my compounds (however, deprotonation of simple substrates with LDA or BuLi still work although I get sometime lower yield than described). Anyway, thank you for your help!

            Comment by N_I — July 27, 2017 @ 8:32 am

          • direct metalation with BuLi or LDA and its variants on your substrate is not a good idea, I would expect N-Boc indole to be more reactive than thiophene. Also, use of halo-substituted thiophene is a much better alternative, with CO and boronic acid. If they wont let you buy CO lecture bottle, you can use W(CO)6 or Mo(CO)6 instead as CO source or better yet, make your own CO by injecting formic acid into sulfuric acid in a separate flask- you only need enough CO to inflate a balloon

            Comment by milkshake — July 27, 2017 @ 11:08 am

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