l-Dromoran (17-methylmorphinan-3-ol)

[HumbleStudent]

So, ok, but a question still remains (for me).

How do they do it at chemical plants?  I mean, I've seen small pharmaceutical companies selling everything from Viagra to DXM.  Surely, if one can synthesize DXM, morphinans will not be too difficult.  What methods are they using?

[Rhodium]

How do they do it at chemical plants?

Evidently, the procedure outlined in the patents posted in

Post 507952

(Rhodium: "Swiss Levorphanol Patents", Methods Discourse) was the route used by Hoffmann-LaRoche, at least a few decades ago. Even if you don't know german you can at least follow the reaction sequence by the illustrations provided.

[HumbleStudent]

Now, I just have to figure out a good way to digest and assimilate all the info into my point-form pre-plan.  

I never thought I would start getting interested in this field so much as I have become.  I have a feeling of how an alchemist might have felt!

Anyway, out of curiosity:
Starting with cyclohexenylethyl amine and p-methoxyphenyl-glycidic acid methyl ester + all the other chemicals, what is the real yield from all the "raw" materials so to speak?

I came up with roughly an yield of 11.6% (disregarding the liquids.)

Can you guys tell me what the yield is, or am I close?

In short, what is the final yield when compared with the amount of all the starting chemicals?

[starlight]

the yield for the preparation of XXXV is missing, therefore the overall yield is impossible to calculate.

[Pimpo]

Hi starlight,
wasn't online for a while, therefore this reply took so long. The yield for XXXV is not stated unfortunately, no idea why.

[HumbleStudent]

Hi Pimpo,
Thanks a lot for the post on the synthesis of Morphinans.

Sounds sweet, eh? Hard to say, how well the conversion from octahydro-isoquinoline/10-hydroxy-decahydroisoquinoline to morphinan really works, but it does look possible!

Have you looked into this anymore?  I mean, do you think it works as well as one would think, or is it plagued with tons of problems that makes the reactions fail and or produce low-yields?

Just curious.

Anywho, thanks!

[ning]

I somehow doubt they actually spent too much time optimizing yields. Total syntheses are rarely intended to be practical production methods.

But then, for some people, they are....

[Pimpo]

Thanks, for appreciating my posts HumbleStudent .
Well, sometimes I think those commercial researchers don't want to make things too easy for their competitors, that might explain some difficulties.
The Pictet-Spengler synth sounds like conditions have to be carefully controlled (Temperature would be no problem on a water bath, but the pH perhaps should be watched electrometrically?), as yields are only so-so at best. The further two steps look easier, then. Would be interesting to find out, if the hydroxy-decahydroisoquinoline could be alkylated with RBr/K2CO3 in DMF like the corresponding octahydro-isoquinolines. Would allow for some variety. I mean the demethylation/dehydration with HBr (and then alkylation) gives too low yields.
This will be further investigated (promise!), but unfortunately this interesting synth had to wait for some time now and there are still some things to be organized .

P.S. It's a shame, that apparently no other bee is doing practical work here . It's such an interesting field!

[HumbleStudent]

After some thought, I've been thinking of dropping the idea of morphinans in the story.  Hey, its a story, so I can take some liberties with exact facts.  So, now it's carfentanil... more exotic, ooooh!

As this is for a book, the protagonist has all the equipment(glove box, hazmat suit, antidote, etc.) 

After using the search engine etc.  I now know a lot.  But, this time I have some questions(silly as always)...
1. Given the synthesis etc. on Rhodium's site.  Would it be possible for a regular (not a wiz) organich chemist (with some experience, and a BSc in Organic Chemistry) to actually make carfentanil?  Or is it extremely difficult?
2. What about administering the compund?  Is it only by IV?  I would think that as it is so minute, it would be absorbed by skin without the need for a needle.

Keep in mind that this is for a book, so I can stretch the truth a little. :-)

Anyhelp will be appreciated.  Thanks.