RobRylan
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Thalidomide synthesis questions
I thought it would be a fun project to synthesize thalidomide, the infamous drug that caused birth defects, and came across this approach on pages
79-80 of this thesis pdf
It requires phthalic anhydride and glutamic acid to be refluxed in pyridine, then the product is reacted with acetic anhydride to form a new ring, and
then it is melted with urea to form crude thalidomide. None of the reactants are difficult to obtain so I'm going to try it out.
A few questions about it though that I've had trouble answering myself (sorry if any have obvious answers I just start org II)
-Is the pyridine for the reaction solvent just used as a higher-boiling polar aprotic solvent or does it play a role in the reaction? If not could
something like methyl ethyl ketone be used with a longer reflux?
-Also, how would the Ac2O be added? Would the N-phthaloyl glutamic acid intermediate be extracted and just reacted with straight Ac2O?
Thanks for any help
Edit: I found information regarding the Ac2O reaction
[Edited on 18-1-2017 by RobRylan]
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Tsjerk
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Step 1 apperently can be done in DMF, the reaction is also stereospecific, although apperently the mocule's enantiomers are not stable as the
stereogenic centre's hydrogen is acidic.
http://sphinxsai.com/Vol.3No.1/chem_jan-mar11/pdf/CT=37(234-237)%20JMCT11.pdf
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