Comments on: 4,6-dimethylpyrimidine-5-carboxylic acid ethyl ester

By: The Futile Cycle » Blog Archive » Interesting Chemistry Quote of the Day

Tue, 13 Mar 2007 16:15:55 +0000

[...] was written before, but I found it today. From Org Prep Daily: On cannot be careful enough when working with methyl triflate. The vapor inhalation can cause [...]

By: milkshake

milkshake — Sat, 03 Mar 2007 19:20:08 +0000

if you don’t cover that OH, you will get only enolate salt formation and no cyclization; heating to bring about dehydratation by brute force does not help because the formamidine starts falling apart at lower temperatures

By: diketene

diketene — Sat, 03 Mar 2007 05:14:17 +0000

Maybe a silly question: why do you need to methylate ethyl diacetoacetate to get the pyrimidine?

By: Milo

Milo — Thu, 01 Mar 2007 01:21:46 +0000

Things are going quite well at company X. I have found that working on 0.5 – 2.0 kg scale to e really scary at first, but once you get the idea that heat is hard to remove and pressure builds up fast, then it is not so bad. I am fortunate in that each project I am on has me learning new chemistry and reactions, some of which I am still shocked they work (like PPA mediated cyclizations). I am still getting used to the fact that the people who dole out the budgets have no idea what I really do. I guess that is business for ya.

I do have a set of models, but they are so cheap… I am actually pushing for a good set of harvard CPK ones. We have the money…

By: milkshake

milkshake — Wed, 28 Feb 2007 06:44:59 +0000

You are right, it is usualy overkill but such hot reagent can have advantage of improved O versus C selectivity (when alkylating enolates), milder reaction conditions or a cleaner reaction mixture. I was making triethyloxonium tetrafluoroborate (the OrgSyn procedure is very easy) and the alkylations with it were a joy to behold – that is, until my triethyloxonium stock solution started decomposing.

I think Magic Methyl has no advantage over MeOTf, it was just popularized before MeOTf became available.

By: Tom

Tom — Wed, 28 Feb 2007 05:43:32 +0000

Milkshake ~ Before magic methyl was pulled from commercial sale, were there any anions or nucleophiles that absolutely required such a reactive methylating agent? It seems as if utilizing magic methyl in many cases would be regarded as sheer overkill.

By: milkshake

milkshake — Tue, 27 Feb 2007 12:09:36 +0000

My career is fine because I am not doing any. I am pretty content – having a good boss and a good project and pleasant and fun colleagues in the lab plus enough research money to buy stuff and a good salary and decent job security for the next few years and laid-back atmosphere – and also I can play little on side with some Pd catalysts, so things can’t get much better.

You are absolutely right, methyl is not optimal, and the formamidine is falling apart in ethanol during the reaction – but I was following a reaction scheme from Astra-Zeneca Bioorg Med Chem Lett paper, and they mentioned 35-50% depending on the amidine so it was not so bad. But sulfonyl should be much better. Maybe less messy to work-up, too. (I had to re-distill the product even after purifying the mix on a fat silica column, so it was little tedious.)

How is your life- from your posts I see that it is not bad at all, at the mysterious company X. Also, do you know one can buy a pretty decent molecular model sets from Aldrich catalog – it is not very precise as computer model minimisation but rotating the bonds to see where they clash is lot quicker

By: Milo

Milo — Tue, 27 Feb 2007 11:57:37 +0000

Oh Ho! Pyrimidines! I have not seen this type of amidine cyclization since my days as a molecular recognition guy. Good stuff. I was always amazed at the chemical shift of the proton on C2, always seemed a little farther downfield than it should be.

Why make the methyl ethyl, why not the mesylate or the tosylate, you might increase the yield of the cyclization (which I always found crappy with non-electron rich amidines).

Thanks for this one.

BTW, How are you not successful in your career? You like what you do and are employable… seems good to me. Life is a whole lot more than just the job.

By: milkshake

milkshake — Tue, 27 Feb 2007 06:29:52 +0000

Tom, thank you for your comment – I wrote the next post as the answer to your question. You know, I am not very succesful in my chemistry career because I screwed up. But I like doing chemistry.

When I hear somebody like Brian Stoltz or Dave McMillan giving lecture and see that what they have done was pretty original and accomplished in a short time, I realize why they are in the first league – and I am not. But one can have fun playing friendly county matches, even if being a pro can be more fun (and fame and money). Once you stop worrying about getting all the way to the top, you can relax and watch the scenery and enjoy the hike.

By: milkshake

milkshake — Tue, 27 Feb 2007 03:50:49 +0000

I didn’t plan on deleting people’s comments – but in this case it felt really good. I think I am gradually getting the taste for it.