underdosed
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Piracetam to Ethyl 2-Oxo-1-pyrrolidineacetate
Hey, im looking to make some pramiracetam from piracetam, as per the synthetic routes in another thread, just wondering if anyone has any idea how to
convert piracetam to Ethyl 2-Oxo-1-pyrrolidineacetate, effectively the acetamide to the acetate. Im thinking a base hydrolysis with ethanol?
Cheers,
Ud
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Some ideas on Piracetam -> Pramiracetam?
I'm going to just copypaste the post I made to sci.chem:
| Quote: | Hi, I have a question regarding amide reactions. I have a molecule that has two amides, a primary and a tertiary, and I want to add a functional
group to the primary amide to make it a secondary amide. I do not however want to affect the tertiary amide.
Specifically, I want to turn this:
http://upload.wikimedia.org/wikipedia/commons/e/e9/Piracetam...
Into this:
http://upload.wikimedia.org/wikipedia/commons/b/b2/Pramirace...
Quite honestly I'm not sure where to start. A reaction I have found online for the total synthesis of pramiracetam is as follows:
Bromoacetic acid reacts with thionyl sulfate to form the acid chloride, then is reacted with ethanol to form the ethyl ester. This ethyl ester is
reacted with the sodium salt of 2-pyrrolidinone, which is synthesized by reacting 2-pyrrolidinone with sodium hydride in toluene and DMSO, in order to
make ethyl 2-pyrrolidone-N-acetate. This is then reacted with N,N-Diisopropylamino ethylamine (CAS # 121-05-1) to make pramiracetam, which is then
reacted with hydrochloric acid to make the hydrochloric acid salt.
If there were some way of turning piracetam into ethyl 2-pyrrolidone-N-acetate or a similar molecule, this setup could be greatly simplified. Anybody
have any ideas? |
I saw there was another thread here about the same idea, but it doesn't look like anyone had any ideas at that time.
So, what do you guys think?
(Edit by Nicodem: Merged with the old thread referenced above and removed the now bogus link.)
[Edited on 14/11/2009 by Nicodem]
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Nicodem
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Threads Merged
14-11-2009 at 09:56 |
Nicodem
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Yes, it should be easy to selectively hydrolyse the -CONH2 of piracetam. This gives you 2-(pyrrolidin-2-on-1-yl)acetic acid which can be coupled with
2-(diisopropylamino)ethylamine to give pramiracetam.
Reflux in 1M NaOH should be enough for the first step. The work up would be a bit annoying due to the high aqueous solubility of the product, but with
some ingenuity it would not be a problem. For the second step you can use CDI amide coupling or just make the acid chloride with oxalyl chloride or
SOCl2 and then react it with the amine. Or you can use the boric acid catalysed coupling of carboxylic acids with amines as described at Organic
Syntheses.
All this however does not make much sense because it would be simpler, more effective and much cheaper to just follow the usual synthesis of
pramiracetam.
[Edited on 14/11/2009 by Nicodem]
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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Checked out all the reagents in sigma aldrich... looks like by far THE most expensive reagent is the N,N-diisopropylamino ethylamine, at $91/100mL 97%
purity. The total synthesis would cost about $784 per 940g, assuming 100% yield. This is cheaper than buying it outright, but still a large amount
of money down.
I wonder if there is a cheaper way to synthesize the N,N-diisopropylamino ethylamine then...
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Nicodem
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If it is about economics, then you can always couple the 2-(pyrrolidin-2-on-1-yl)acetic acid with ethylenediamine (61.10EUR/1L) and then reductively
isopropylate with acetone, H2 and Pd/C. Even though you would need an approximately fourfold excess of ethylenediamine to prevent diacylation, it
would still be the cheaper, particularly since ethylenediamine can be obtained even cheaper in bulk and the excess can be recycled (with the boric
acid method recycling would be very easy). This would however add another step in the synthesis.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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DJF90
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I suppose you could say its a matter of what is more abundant, time or money. If you have the time to make the reagents/go a longer route, and if it
saves you money, then why not? Sure it might be a bit of a "bother" but at the end of the day its all fun chemistry right?
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mr.crow
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You could synthesize the N,N-diisopropylamino ethylamine by blocking off one of the amino groups of ethylene diamine with phthalic anhydride, then
alkylating the other one.
Can you form the amide with the acetic acid derivative, or do you need the acid chloride like the original procedure?
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Z8320
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Quote: Originally posted by Nicodem  | | If it is about economics, then you can always couple the 2-(pyrrolidin-2-on-1-yl)acetic acid with ethylenediamine (61.10EUR/1L) and then reductively
isopropylate with acetone, H2 and Pd/C. |
Is a high pressure palladium catalyzed reduction really necessary for this particular reductive amination? Would, for instance, hydrides or even
aluminum amalgam not suffice? I don't really know enough about the reaction to answer it myself, but I don't think I'll ever get around to building
that hydrogenator I've always wanted, so I thought I'd ask.
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