Sinteza metilfenidata (Ritalina)

[cokemuffin]

Torej bi bil postopek tak, da bi ritalin hcl dali v raztopino NaOH, dobili ritalin freebazo in nato le to dali v ipa, da bi dobili izopropilfenidat? Domnevam, da je treba hcl dodati po esterifikaciji, da se OH karboksilne skupine ne nadomesti s Cl, vendar nisem 100 % prepričan o tem.

 

[G.Patton]

Pozdravljeni, opravičujem se za dolg odgovor. Vašega vprašanja nisem videl.
Ne, eterefikacija ni delo, kot ste ga opisali. Pridobiti morate natrijevo sol ritalinske kisline in nato v kislem stanju z IPA pridobiti ester.
To ne bo delovalo, kot ste povedali =) Kakšen je razlog za te manipulacije? Pravzaprav nisem prepričan, da bo reakcija uspešna. Poleg tega boste izgubili del svojega ritalina.

 

[TheNut22]

Kadar sinteze vključujejo cianide, grem v lokalno trgovino s strojno opremo na oddelek za bazensko kemijo in po Na DCCA ali TCCA. Z njimi se izvede enaka reakcija kot z bolj strupenimi oblikami cianidov. Tolikokrat sem iz DLPA naredil fenilocetno kislino in tako naprej ..

 

[edogawaconan]

Hey.. where do they sell cyanide. I am looking for gold electric stripping but could not find any legit marketplace

 

[dupskoslonia]

Hej, fantje. Imam ritalinsko kislino. Kaj potrebujem za izdelavo metilfenidata in etilfenidata? Sem popoln novinec, ali mi lahko razložite korak za korakom? Bila bi vam zelo hvaležna.

 

[kotkata]

Ali obstaja kakšen protokol ali priročnik za začetnike ali recept za pretvorbo ritalinske kisline v metilfenidat?

Po mojem razumevanju to ni raketno, vendar sem nekoliko zmeden, kako iz ritalinske kisline dobiti metilfenidat.

 

[SmartResearcher]

Pozdravljeni vsi! Odgovor za dupskoslonia, dodajam recept za metilfenidat hidroklorid iz dl-treo-ritalinske kisline (ki je enostavno dostopna na Kitajskem, cena za 1 kg je približno 600-700 $). Po tem receptu sem nekajkrat izdelal dl-treo-metilfenidat hidroklorid in je popolnoma enostaven in popoln. 1 kg metilfenidat hidroklorida lahko pripravite v 20-litrski bučki z enim vratom (ne potrebujete reaktorja).

125 g (0,57 mol) dl-treo-ritalinske kisline, dodane v reaktor. Nato dodamo 256,7 g (5 mol) dimetilkarbonata in 27,5 g metanola. Nato se pri sobni temperaturi z mehanskim mešalom (magnetno mešalo ni primerno za to operacijo) počasi doda 762 g 96 % ali več žveplove kisline (temperatura <80oC). Temperatura plašča se je povečala na 85oC (ciljna notranja temperatura približno 70oC). Reakcija se je mešala čez noč (vsaj 16 ur) pri temperaturi plašča 85oC.

Nastalo zmes smo nato ohladili na 15-20oC. Nastali mešanici smo dodali 250 g izopropil acetata in nato 18 % NaOH (212,5 g, 1,68 mol), pri čemer smo temperaturo vzdrževali na 30oC. Nato se je zmes mešala približno 15 minut. Plasti so se usedale približno 20 minut, spodnja, jedka (vodna) plast pa se je ločila in zavrgla. Organski plasti smo nato dodali deionizirano vodo (187,5 g) in zmes mešali približno 20 minut. Plasti so se usedale približno 20 minut, spodnja, vodna plast pa se je ločila in zavrgla. Organska plast je vsebovala dl-treo-metilfenidat.

Drugi reaktor smo napolnili z raztopino 37% HCl (59 g, 1,05 mol) in IPA (250 g). Notranjo temperaturo raztopine smo nastavili na 55oC. V ta reaktor se je nato v 90 minutah z dodajnim lijakom dodala organska plast, ki je vsebovala dl-treometilfenidat, pripravljen v POSTOPKU 1, pri čemer se je temperatura ohranjala na 55oC. Nato smo zmes ohladili na 10-15oC in jo mešali 30 minut. Nastalo suspenzijo smo filtrirali skozi Buchnnerjev lijak, mokro pogačo pa sprali z IpOAc (125 g). Pridobljenih je bilo približno 110-125 g dl-treo-metilfenidat hidroklorida (popolnoma enakega izomera kot v farmaciji).

 

[kotkata]

Super, najlepša hvala, @dupskoslonia!

Resnično cenim!!

 

[untryrgos]

Pozdravljeni, hvala za vaš način sinteze. sledil sem vašemu načinu in pojavilo se je nekaj razlik. ko sem se prepričal, da vse kisline izginejo, in končal prvi korak, sem našel toliko ločevanja soli. Ali gre za metilfenidat sulfat? pH je približno 1 do 2.

 

[HerrHaber]

Metilne estre v prisotnosti amino skupine zlahka dobimo tudi z delovanjem klorotrimetilsilana v metanolu z veliko prijaznejšo pripravo, vendar so po drugi strani stroški verjetno večji in mislim, da tudi izkoristki (te je treba primerjati). Etilfenidat in izopropilfenidat imata veliko večjo rekreacijsko vrednost (in dolgotrajnejši močnejši učinek) Ne morem si kaj, da ne bi razmišljal o uporabi biokatalize z različnimi alkoholi in NOVOZYME bi moral biti prva izbira, večino encimskih esterifikacij in transesterifikacij se najprej poskusi s tem ekstremofilnim (Candida Antarctica) encimom, ki se izloča v zunajcelično okolje, zato ga je lažje pridobiti. Najbolje je, če je encim imobiliziran na trdnem materialu (pogosto superparamagnetni nanodelci Fe3O4, funkcionalizirani na površini z encimom, ki je povezan z nekim organokromnim vezivom), saj jih je mogoče filtrirati in ponovno uporabiti, magnetne pa je še lažje predelati. Z veseljem bi poskusil s tem v majhnem obsegu, za kar bi zadostovalo 50 g ritalinske kisline, kar je verjetno pod običajnim MOQ. Menim, da so zelo zanimivi tudi naftidati, vendar se lahko izvedba celotne sinteze izkaže za težavno.

 

[BlueDex]

I tried ethylphenidate (the ethyl version of methylphenidate) in the past and it calmed me down, but it felt like a riddle in my mind and it was kind of crappy. I tried Modafinil, Armodafinil, and Adipex-75 and they're also relaxing, but cleaner and it didn't feel crappy but it felt better, and I prefer those to Ethylphenidate.

 

[Osmosis Vanderwaal]

Interesting note, the name Ritalin came from the chemists wife's name, Rita. Nobody in the world says this correctly except you and I

 

[DrDoom]

What is the recipe for 4-fluoro-methylphenidate (4f-mph)? The 4f substitution makes it more potent.

 

[lamename69]

I've read that the only absolutely needed elements for the simplest MPH synthesis are ritalinic acid, methanol and HCl or H2SO4. Is this really enough? If so, what quantities are best used? For example, using 0.1 mol ritalinic acid, do I need only 0.05 mol H2SO4 or a bit more since it serves as a catalyst? Or should I rather look at the concentration of the H2SO4 in the methanol. I've had problems with using bigger amounts of methanol because the ritalinic acid simply wouldn't dissolve in it. It did only after adding more H2SO4 or evaporating most of the solvent. I haven't tried it with HCl so I don't know if it's the acid or water concentration. I might buy acetyl chloride to find out though. I did create the product and isopropyl- and ethyl- too, although I am not sure about the basis of some of my actions. 12-24 hrs at 40'C. I will have my creations tested in GC/MS in a while but until then I'd like someone knowledgeable to comment.

 

[hghisnice]

The synthesis is actually really simple. A sample of RA is added to an RBF with a mag. stirrer. You then add a random excess of methanol to somewhat dissolve, although this reaction likely occurs to a large extent in the solid form (make sure to thoroughly crush). A few drops of HCl is added and then refluxed. This will have rather low conversion in the end, so it's also instead advisable to use p-TsOH and an ultrasonic bath instead.

 

[lamename69]

That's great, I didn't suspect that the reaction could take place in solid form. I thought that I needed to add excess acid in order to dissolve the RA. Thanks.

 

[Chemtrail]

US20150051400A1

A process for the preparation of methylphenidate hydrochloride and its intermediates thereof

US20150051400A1 - A process for the preparation of methylphenidate hydrochloride and its intermediates thereof - Google Patents

The present invention relates to an industrially feasible and economically viable process for the preparation of methylphenidate hydrochloride of formula I and its intermediates thereof.

patents.google.com

Uses this starting precursor:

2-phenyl-2-(piperidin-2-yl) acetamide

 

[Chemtrail]

Another one:

WO2012080834A1 - Low-temperature synthesis of methylphenidate hydrochloride - Google Patents

The present invention describes a process for the preparation of methylphenidate hydrochloride. The process involves the esterification of ritalinic acid and methanol in the presence of an acid catalyst at a low temperature. The process may optionally involve the addition of an orthoester.

patents.google.com

Low-temperature synthesis of methylphenidate hydrochloride

WO2012080834A1

The method of claim 1 , wherein the salt of ritalinic acid is threo ritalinic acid hydrochloride.
The method of any one of claims 1 to 2, wherein the salt of methylphenidate is threo methylphenidate hydrochloride.


These patents are must reads

 

[Osmosis Vanderwaal]

Ritalin was before Mt time, no kids had Ritalin when I was a kid, when I was about 20, I started hearing about it. Fun fact, "ritlin" was names after the inventors wife , Rita and the correct pronunciation reflects "Rita-lin" NOBODY pronounces it right that I know of

 

[Stao]

Hey Guys, I figured I would get my hands a little dirty, You guys: Mainly: smartresearcher.24281 said you can buy dl-threo-ritalinic acid (which is easy available in China, price for 1 kg is about 600-700$)
My Question is Where?
I see a lot of Ritalinic acid CAS No. 19395-41-6 for 700usd for 1 kg
but not alot of
DL-threo-Ritalinic Acid CAS No : 54593-31-6

Same thing?​