Aight, I didn't find an appropriate thread for this, so here goes:
Acetone-->1,3-Dichloroacetone (There's a patent on this using iodides)--NaCN-->1,3-Dicyanoacetone-->reductive amination with aniline-->amide by acetic or propionic anhydride-->dialdehyde (by Stephen aldehyde synthesis, my coup de grace) --reductive amination with phenylethylamine-->fentanyl or its derivatives
Any obvious mistakes I didn't get? Any thoughts?

Helgoland

Found the patent: http://www.freepatentsonline.com/4251467.pdf
Also maybe interesting: http://www.freshpatents.com/Process-for-preparing-13-dibromoacetone-1-3-dichloroacetone-and-epichlorohydrin-dt20081009ptan20080249324.php

Does anyone know how Marquardt used to make 3-methylpiperidone?

Helgoland

 I made a graphic, let's see if more people will post then
Btw, here's the Stephen aldehyde synthesis:
http://en.wikipedia.org/wiki/Stephen_aldehyde_synthesis
I hope this helps.

Helgoland

I know, I made it
The Petrenko-Kritschenko piperidone synthesis won't work for the unsubstituted piperidone; that was discussed at Sciencemadness, I think.
Seriously, an anhydride will attack a nitrile? Didn't know about that.
Reductive amination of amides... About that neither.
Is it fixable/tolerable? If yields were to go down only slightly, side reactions wouldn't be that bad.
Otherwise - a protecting group for the carbonyl might be the thing we're looking for. Would acetals
survive the Stephen?

Helgoland

P.S. I think the old synthesis wasn't that awesome either, but I could be wrong.

Reactions don't just magically target the particular instances of groups you want them to target.

timecube, they do go exactly the way you want them to when you discuss them but, when you actually perform them, harsh reality sets in.

Easier way to 1,3-dichloroacetone: dry distillation of chloroacetates?
Or would some polyester form?

Also, an aldehyde won't attack a tertiary amine because formation of the necessary imine is impossible (pentavalent nitrogen does not exist).

The intermediate amine in the last step is secondary isn't it? Or did you mean timecubes amide amination-but I think he meant the carbonyl group.
Seriously, dry distillation (or some other way of coupling) of chloroacetates? Anyone?

Helgoland

EDIT: Even simpler would be creating dicyanoacetone from 3-oxoglutaric acid which can be made from citric and sulfuric acid.
        On dry distillation: Doing it with 2-cyanoacetates might be a good idea as well.
One more EDIT: Epichlorohydrine + Cl^- --> dichloropropanole -->--> NPP -->--> fentanyl