Comments for Org Prep Daily

Comment on 1NMPP1 by umesh

umesh — Sat, 28 Nov 2009 05:15:55 +0000

One of my frnd (sr. research colleague), did prepare some derivatives of allopurinol and I think he did prepare so many derivatives of pyrazolopyrimidines starting from 2-cyanoacetamide…

Comment on 1NMPP1 by milkshake

milkshake — Wed, 25 Nov 2009 22:25:10 +0000

Its from a JACS paper that deals with animal biology. The paper does not contain any synthetic experimentals, only a scheme (without yields and without reaction condition details) but provides a reference to J. Chem. Soc. Perkin 1 paper – which does not have this particular compound either. Then there is a recent patent which does describe similar compounds but again not this one. My problem was that all detailed procedure precedents in the literature have aryl directly linked, there were no examples with benzylic substituents so I worried about the regiochemistry a bit. The main change is using MeOTf in MeCN – I knew from another example (2-acetyl-Et-acetoacetate O-methylation) that this shoudl work. I don’t like dimethyl sulfate 5 eq. reflux which they used in the Perkin paper, and we did not have tons of TMS-diazomethane at hand, the reagent they used in the patent.

Daniel: you are wasting your time by using wet ether, ether distills very nicely, just add a spoon of LiAlH4 to your old stuff and distill it over from a warm bath under Ar for your purpose. Old Li crust can be scraped off or cleaned by dipping it in methanol and drying. It darkens fast because of the reaction with air. Use Ar, not nitrogen. Old bromobenzene should be fine but it won’t hurt you to re-distill it – it builds your backbone. If you want to be sloppy go to peptide chemistry.

Comment on 1NMPP1 by Jonez

Jonez — Wed, 25 Nov 2009 16:38:59 +0000

Milkshake:

Did you envision this synthesis yourself?

Comment on 1NMPP1 by Daniel

Daniel — Wed, 25 Nov 2009 15:38:37 +0000

Thank you very much Milkshake, worked perfectly. I’m now trying to react it with phenyllithium, made in situ from decades-old lithium block and decades-old bromobenzene, using non-distilled, non-dry ether, in air. Am I wasting my time? It’s truly hard to do chemistry in a biology lab!

Comment on Setting up a vacuum manifold by milkshake

milkshake — Tue, 24 Nov 2009 17:49:52 +0000

It is difficult for me to recommend a particular catalog # because it has been 5 years since I have been setting up mine and I don’t have the original catalog numbers anymore. What you need is a tubing that is as wide as possible while fitting the manifold (and cold trap) and sufficiently thick-walled as to not to collapse under vacuum. An approximate rule for the wall thickness of vacuum tubing is that the wall should be about one half of the INNER diameter of the tubing (=the hole)

Comment on 1NMPP1 by milkshake

milkshake — Tue, 24 Nov 2009 17:41:16 +0000

Its for a friend of my friend who even does not work here, so I don’t know all the details. If I understand it correctly it is used for a very specialized assay that requires mutant animals/mutant cell lines. The compound hits only the mutant – it does nothing to normal cells. Not too many people run this assay because the engineered animal stuff is hard to get, and it is good only for one particular signaling pathway. I suppose the worldwide consumption can be like 1 g a year, which is only few thousand USD (I think the lowest price I saw online was $880/100mg)

Comment on Setting up a vacuum manifold by Bob

Bob — Tue, 24 Nov 2009 16:22:48 +0000

Great post! Definitely helped me a lot in the past, and think it will in the future. After using all our PVC tubes ordered by my predecessor, I’m finely up to ordering some tubing myself. Helped by the fact that the previous tubing is not available anymore, I went somewhat deeper into other tubing. In the inorganic laboratory, they switched to Tygon tubing, but of a type I have some doubts about. They use the B-44-4X type (see http://www.tygon.com/tygon-b444x-tubing.aspx). Is this the type you recommend, or does it have some downsides. I would think the R-3603 type is more the way to go (see http://www.tygon.com/tygon-r3603-lab-tubing.aspx) but this one is also more expensive. (I think there’s also some marketing involved with all the different tubings they have)
The inorganic laboratory is using the B-44-4X type for a month now, without any complaints. How do you comment on that?

Thanks in advance.

Comment on 1NMPP1 by Ed

Ed — Tue, 24 Nov 2009 14:53:19 +0000

If 1NMPP1 is so expensive, have you considered selling some of those 6g? Could raise some funds for the Christmas party!

Comment on 1NMPP1 by marto

marto — Tue, 24 Nov 2009 12:03:22 +0000

Greetings MS,

I am doing cyclization reaction of 1,3 diketones (both keto group have got similar reactivities ) with methyl hydrazine. I get both regiosomers with equal amount. Its difficult to characterize the two regisomers. Is it worth doing 1H – 13 C correlation ..If you can suggest any other NMR/analytical techniques would be really helpful.

Thanks

Marto

Comment on One phosphine to rule them all by milkshake

milkshake — Mon, 23 Nov 2009 21:55:08 +0000

I noticed that they typically use their hindered biaryl phosphine ligands on new arylation reactions empirically – they test maybe five different ligands and two or three different bases and two different solvents until they get some acceptable result. The problem with choosing the right ligand for Pd is that the complex has to perform several transitions one after another to turn over, and the rates of each step in the catalytic cycle can go wrong if the ligand substitution is not optimal – the actual influence of the phosphine substitution is hard to guess with untested system. So they start with some reasonable precedent and guess about what factors are important, and they go on by trial and error