N-phenethylpiperidone :

8g of 4-piperidone hydrochloride monohydrate (52 mmol) , 9.65 g of phenethyl bromide (7.1 ml ; 52 mmol ; 1 eq) and 21.5 g of potassium carbonate (3 eq) are added into 75 ml anhydrous acetonitrile. The solution is stirred vigorously with a magnetic stirbar at 25 °C for 2h. The suspension is heated to 45°C for 4h, then refluxed for 16h. The light pink suspension is cool down and filtered with a buchner, the cake is washed with 20ml acetonitrile and the solvent is boiled off with a rotavapor. The brown oil cristallises at RT to give 11.0 g (104 % ) of honey-like amber cristals.

The purification is tricky. Several solvent have been tested and gave no acceptable result... The impurities seems soluble in iPrOH, Et2O but not in petroleum ether. The product is soluble in hot petroleum ether and cristallises out when put in fridge. One part is cristallised from diethyl ether to give 2.3 g of beige cristals ( mp = 58°C ). Petroleum ether was added to the second part of honey cristals and heated until all the cristals are dissolved. The impurities form a non miscible dark orange oil wich can be separated out. The milky ether phase is separated out and the operation is repeated again to get as much product as possible. The two ether soluions are put in the freezer. 1 hour later beautiful white cristals (5.1 g ; mp = 55°C) are recovered with a spatula. The cristals are not filtered because some yellow cristals are still present at the bottom. Theses cristals are cristillised again from petroleum ether to give 3.4 g of white powder ( mp = 60°C !!) after cooled at -5 °C. Yield after purification : 60-70 %.

Proposition for purification :

The crude product is dissolved in hot petroleum ether (large volume). The bottom brown oil is separated out. The petroleum ether is rotavapored and the resulting cristals are cristallised from Et2O or another suitable solvent.

Syntesis improvement :

The phenethyl bromide can be added dropwise to avoid quaternisation of the piperidone.

I hope Dr.Methoxy still visits here, I would imagine he is using the route from Rhodium;

http://orgchembase.com/archive/Rhodium/chemistry/fentanyl.html

There has been quite a large improvement on that synth, please look at;

A METHOD FOR THE PREPARATION OF FENTANYL
WO/2009/116084
GUPTA, Pradeep, Kumar

The invention provides a method for the preparation of fentanyl comprising: (a) reacting 4-piperidone hydrochloride (NPP) with aniline in presence of reducing environment to produce 4-anilinopiperidine (4- ANPP), (b) alkylating/reacting the 4- ANPP as obtained from step (a) with phenethyl halide under reflux conditions in highly alkaline medium to give 4-anilino-N-phenethylpiperidine, and (c) converting the said 4-anilino-N-phenethylpiperidine to fentanyl by reacting with propionyl chloride in presence of halogenated hydrocarbons then isolating fentanyl by solvent extraction and purified by crystallization from petroleum ether (60-80 °C).

http://www.wipo.int/pctdb/ja/wo.jsp?WO=2009116084&IA=IN2009000159&DISPLAY=STATUS

it can be downloaded at espacenet also, The reducing enviroment being zinc in acetic acid.

alkylated piperidones are the way to go not many mentions in the literature because this route is'nt taken by big pharma it's taken by evil chemists for sake of convenience.

big pharma likes to keep it cryptic for the recipie cooks also the obvious mistakies and the ususaul deviations from the time/temp parameters. the "term skilled in the art" aptly describes this plus patents are'nt peer reeviewed.

Fantastic, now lets work on OTC phenethyl bromide and OTC piperidone hydrochloride.  Also, substitution of reaction solvent might give better results.  For some reason, I'm thinking DMSO or DMF.  Someone tell me why I'm wrong hahaha

Well hypochlorination of Styrene gives predominantly the 2-chlorohydrin (If you google it you'll get the PDF of a paper from the Canadians that did it) so that would give the a-hydroxy-variant fairly rapidly, albeit probably not in the yields you'd see from the bromo variant.

Fantastic, now lets work on OTC phenethyl bromide and OTC piperidone hydrochloride.  Also, substitution of reaction solvent might give better results.  For some reason, I'm thinking DMSO or DMF.  Someone tell me why I'm wrong hahaha

PhenEthyl Bromide can be replaced with easier reagent. Piperidone synthesis can use close of any substituted ketone and aldehyde. One can substitute a amine also.

I suggest triacteoneamine in today and Methylated PhenylPropanolAmine was from Pugsley but is base on Drone #342.

There is many chance for substitution but who know of potency if it happen? It change with compound.

In the Indian patent metioned above what the heck is "100% aqueous sodium hydroxide solution?"

Quote from patent:

Step II: Preparation of 4-anilino-N-phenethyIpiperidine:
In a round bottom flask, lto 5 parts (w/w) of 4-anilonopiperidine preferably 2 to 3parts (w/w)prepared in step 1, 0.5 to2.00 parts (w/w) of 100%aqueous sodium hydroxide solution preferably 1 to 3 parts (w/w) and 2 to 10 parts (w/w) of 2- phenethylbromide, preferably 4 to 6 parts(w/w) were taken. The reaction mixture was heated with stirring at 80 to 15O0C preferably at 100 to 13O0C for 2 to 10 hrs preferably 3 to 7 hrs. The reaction mixture was then poured in the ice cooled water and crude product 4-anilinophenethylpiperidine was obtained by filtration. The crude product was recrystallized with chloroform-petroleum ether (40-600C) to give 4-anilino-N-phenethyl- piperidine, mp 98-1000C.

an idea for 4-piperidone:

An ammonium salt of a dicarboxylic acid, when heated, will cyclize to the relevant imide, if such cyclization produces a 5- or 6-membered ring. If you do this with acetonedicarboxylic acid, or it's reduced form isopropanol-1,3-dicarboxylic acid, both of which can be produced from citric acid, you get the imide, either 2,4,6-trioxopiperidine or 2,6-dioxo-4-hydroxypiperidine, same basic idea, slightly different compounds. A "strong enough" reducing agent like zinc borohydride should reduce the imide to an amine. Hell, zinc dithionite might work.

http://books.google.com/books?id=lg2r9BDlbM8C&pg=PA524&lpg=PA524&dq=ammonium+succinate+pyrolysis&source=bl&ots=RXeo8QuVYN&sig=QAx_YojerJQ2L2gX19HvhTS269U&hl=en&ei=Yzn7TIfqN4S8lQeQ4eyPDA&sa=X&oi=book_result&ct=result&resnum=1&ved=0CBgQ6AEwAA#v=onepage&q=ammonium%20succinate%20pyrolysis&f=false