El_Zorro (Hive Bee)
07-10-02 23:30
No 330970
      Cocaine-->WIN35,428  Bookmark   

This was started in the General Discourse forum, but I thought it could use some dicussion on the actual synthesis.

Now, the first step is to clean ordinary street coke.  Rhodium said he had some solubility data stashed away, I bet that could be useful.  But most helpful of all would be first hand A/B procedures that go farther than turning it into crack.  I would think that a NP wash, then dumping it in ammonia water until the freebase had precipitated, then extracting with Et2O, then acidifying with concentrated HCl, and diluting with Et2O until it all precipitates would give almost pure cocaine.

But then, what if it's cut with something like powdered novacaine or lidacaine?  Would those make it through the A/B?  I guess this is where the solubility data would come in handy.

Now, once the coke has been cleaned, the next step is to reflux in HCl(MeOH), according to Post 329415 (Rhodium: "I feel there are TOO many coincidences now...", General Discourse).  I guess this is just an acid hydrolisis of the ether bond between the tropane ring and the benzoate moiety thing.(Is this the weak point that reqires a weak base be used to turn cocaine into freebase?)  So that leaves you with Anhydroecgonine Methyl ester, which can be distilled at 67-74C (0.1mm), according to ../rhodium/djvu /clarke.djvu.  Peachy.

Now, the final step would be to run a grignard on the Anhydroecgonine Methyl ester with (p)flouro-bromomagnesiumbenzene, which leaves you with the desired analog as the major constituent.

The final step is the only one that I have questions about, really.

1)Well, the grignard with the (p)flouro-bromobenzene is what I'm worried about.  How do you keep the F from snagging a Mg atom?  It's a halogen, too, so what keeps it from reacting?

2)So the products are distilled after the reaction, or do you just A/B?  Reasons?

3)What would be a good recrystallization solvent for this end product?


Just as a side note, if this were to be cut back 50x to normal coke strength, would that prevent it being rock up into crack?  Depending on what cut you used, right?  This could be a very good thing for the coke market, from some points of view, anyway.  Not only would it last longer, It might eliminate the manufacture of crack.  But then the CIA might get pretty pissed that you were killing their principle product.cool

Do not go gentle into that good night.  Rage, Rage, against the dying of the light.  --Dylan Thomas
 
 
 
 
    lugh
(Moderator)
07-11-02 02:45
No 331068
      Merck Process  Bookmark   

A simpler approach to halo-cocaines would bee to alter the Merck Process, using para chloro/fluoro benzoyl chloride with sodium carbonate/pyridine for the benzoylation after hydrolyzing l-cocaine to l-ecgonine, and estrfying with methanol laugh
 
 
 
 
    Rhodium
(Chief Bee)
07-11-02 05:07
No 331123
      parahalophenyltropanecarboxylates!  Bookmark   

No lugh, we are talking about WIN 35,428 ( Methyl 3-beta-(4-Fluorophenyl)tropane-2-carboxylic ester ) and not the para-halococaines. The general process for their manufacture is outlined below:



Fig 1:
Cocaine (left), Anhydroecgonine Methyl ester (mid) and the analog WIN35,428.
 
 
 
 
    El_Zorro
(Hive Bee)
07-11-02 15:14
No 331255
      So help me out on the last step, Rhod.  Bookmark   

So help me out on the last step, Rhod.  Would the grignard work on (p)flouro-bromobenzene without reacting with the F?  Or could SWIM just use bromobenzene and then run the para-flouronation procedure on the product?

And another thing, does anyone have refs of things like Br and I or MeO or Me groups being attached to the para position that the F is in?  I was thinking that this could be the influential position on that molecule when it comes to psychoactivity, much like the 4 position on the phenethylamine molecule that Shulgin found to be the deciding factor when it came to potency.  Maybe switching the F with Br could increase potency even more.

Do not go gentle into that good night.  Rage, Rage, against the dying of the light.  --Dylan Thomas
 
 
 
 
    Nemo_Tenetur
(Hive Bee)
07-11-02 15:30
No 331259
      para-fuoro is the most active ...  Bookmark   

para-fuoro is the most active compound, chlorine bromine or any othe substitution reduces activity. Only the the para-fuoro-analog without the methyl group on the nitrogen is abt. same potency as CFT.
 
 
 
 
    flipper
(Hive Bee)
07-12-02 20:16
No 331776
      doing it  Bookmark   

If SWIM is gonna perform this synth Does he have to follow the general procedure described in the the djvu file?
(1 mole grignard reagent/0,5 mole anhydroecgonine methyl ester in Et2O. N2 atmosphere, -20C ((Compound 13, -10C )) )

I think that compound 13 is Win 35,428. In the table on page 1262 I don't see a yield. So what is the yield?
And why and when is for compound 13 Cu2Cl2(7 mol %)?

How can be avoided that compound 14 also is formed in the reaction and if it can't be avoided isn't there a easier way to seperate the two compounds? 
 
 
 
 
    flipper
(Hive Bee)
07-13-02 11:42
No 332018
      What will be cheaper  Bookmark   

using cocain to make anhydroecgonine methyl ester or doing Patent EP1127887 (http://l2.espacenet.com/espacenet/viewer?PN=EP1127887&CY=gb&LG=en&DB=EPD) ?
 
 
 
 
    Nemo_Tenetur
(Hive Bee)
07-16-02 09:22
No 333179
      methyl cycloheptatriene carboxylate is the problem  Bookmark   

The anhydroecgonine methylester synthesis is nice, but the cycloheptatrienecarboxylic acid is the problem. AFAIK, there is absolutely no commercial source. You have to synthesize it from diazoacetic acid ester which is also hard to get. You can get the ethyl ester, but not the methyl ester. This requires an ester cleavage and re-esterification. Much work, this theoretically appealing synthesis is impractical frown.
 
 
 
 
    SPISSHAK
(Hive Bee)
07-19-02 06:06
No 334424
      go the practical route.  Bookmark   

If you want a coke analog that works, try 2-hydroxycocaine from aspirin chloride and ecgonine methylester.
Then transesterify with methanol to get 2-hydroxycocaine.
I hate cocaine though damn near killed me many times.
SWIM used to play with Cartel de Jaurez if ya know what I'm saying SWIM saw them today when SWIM went to court on some misdeamenors my homeboy and the whole gang was there on some murder case SWIM did'nt ask details.