Assyl has wondered why this has not been discussed on this board. Acetonedicarboxylic acid is easily prepared from citric acid and conc. sulfuric acid at 0C:
hxxp://orgsyn.org/orgsyn/pdfs/CV1P0010.pdf
Borrowing from Robinson's famous tropinone synthesis, the backbone of this beautiful molecule probably could be assembled in one trivial step from the calcium salt of acetonedicarboxylic acid, formaldehyde, and phenethylamine hydrochloride (dietary supplement).
hxxp://tropane.lab-q.net/synthesis/syn_tropine
It seems keeping the pH around 7 may help minimize the formation of tar from enol condensation. The next big question becomes when to decarboxylate this skeleton. If done immediately, decarboxylation will be trivial, but tar formation may be a problem. If done after reductive amination with aniline, it will be more difficult but the formation of tar could be avoided. It would probably require experimentation to determine the best course of action here. Either way, once this issue is resolved, the rest of the synthesis becomes almost a joke, especially thanks to jon's breakthrough OTC synthesis of propionic anhydride from sodium pyrosulfate and calcium propionate. Aniline could come from hydrolysis of everyone's favorite animal repellant, followed by decarboxylation. Can't remember for sure, but Assyl believes that a methyl on the aniline doesn't affect potency much, so it may also be possible to lazily nitrate toluene and hit it with Fe/HCl, using toluidine instead.
An important question is whether alpha-methyl fentanyl or alpha-methyl-beta-hydroxyl-fentanyl is more euphoric than plain ol' fentanyl. Both of the former are at least longer lived than the short acting fentanyl, which is a huge asset. No one likes dope with no legs.
Thoughts?
hxxp://orgsyn.org/orgsyn/pdfs/CV1P0010.pdf
Borrowing from Robinson's famous tropinone synthesis, the backbone of this beautiful molecule probably could be assembled in one trivial step from the calcium salt of acetonedicarboxylic acid, formaldehyde, and phenethylamine hydrochloride (dietary supplement).
hxxp://tropane.lab-q.net/synthesis/syn_tropine
It seems keeping the pH around 7 may help minimize the formation of tar from enol condensation. The next big question becomes when to decarboxylate this skeleton. If done immediately, decarboxylation will be trivial, but tar formation may be a problem. If done after reductive amination with aniline, it will be more difficult but the formation of tar could be avoided. It would probably require experimentation to determine the best course of action here. Either way, once this issue is resolved, the rest of the synthesis becomes almost a joke, especially thanks to jon's breakthrough OTC synthesis of propionic anhydride from sodium pyrosulfate and calcium propionate. Aniline could come from hydrolysis of everyone's favorite animal repellant, followed by decarboxylation. Can't remember for sure, but Assyl believes that a methyl on the aniline doesn't affect potency much, so it may also be possible to lazily nitrate toluene and hit it with Fe/HCl, using toluidine instead.
An important question is whether alpha-methyl fentanyl or alpha-methyl-beta-hydroxyl-fentanyl is more euphoric than plain ol' fentanyl. Both of the former are at least longer lived than the short acting fentanyl, which is a huge asset. No one likes dope with no legs.
Thoughts?
