quetzalcoatl, what references did you find about doing it?

http://www.erowid.org/archive/rhodium/chemistry/indoleaceticacid.html

References, reguardless of how easy they are to find are always nice to give so we know you saw them....

if you didn't see that link.. tsk tsk

There is a lot of info about making it, however that doesn't mean there isn't another way with IAA or a better modified way. Anyways, it jut never hurts to google a bit first
welcome to TV.

What would happen if you ran it threw an Akabori with alanine just like benzaldehyde to PPA? Would you get something like this?

US4062869 -> U.K.  Patent Specification No. 1,375,836.  The compounds of formula I may also be converted to the 2-(indol-3-yl) ethyl halides using hydroxyl/halogen exchange reagents, e.g. to the bromide using PBr.sub.3 ; which compounds may then be used to prepare therapeutically active compounds as described in U.K.  Patent Specification No. 1,218,570, corresponding to U.S.  Pat.  No. 3,527,761.  By "a hydroxyl/halogen exchange reagent" is meant a reagent capable of displacing the hydroxyl group of an alcohol by a halogen atom.  Typical examples are PBr.sub.3, PCl.sub.3, sulphonyl chloride, etc.

Most of the earlier schemes I had been working through turned out to be rather poorly thought out.

I don't really like starting out with the plain carboxylic acids because whatever you do to them, you're always going to end up with some leftover hydroxyl or aldehyde you then have to get rid of.

If you can source indole, the C-3 position (the one we're after) is relatively easy to add to, and as luck would have it there is an OTC supplement called DMAE (2-dimethylaminoethanol, or dimethylethanolamine) which is cheap, readily available, and pretty much exactly what we would want to add.

I could have sworn I saw a reference at some point showing that indole reacts with primary alcohols and goes through a rearrangement to alkylate C-3.  That wouldn't make much sense to me, but I remember it not making much sense when I first saw it.  I haven't been able to find the reference again, so I may have just misread something.  If that's a real reaction of indole, someone please let me know.

[Edit:  I believe I was looking at the synthesis of indole-3-acetic acid, although I'm not sure if the same reaction is applicable here.
http://en.wikipedia.org/wiki/Indole-3-acetic_acid]

If that isn't a real reaction, I believe DMAE should be halogenated and made into a grignard without too many problems, and then added to indole to give what you want.  I've had a lot of trouble finding indole, though.  It's not listed but occasionally rumored to be watched.  It just doesn't seem to have many commercial uses.  You can probably find it if you look hard enough.


Decarboxylating tryptophan I believe turned out to be a bust due to the cyclization potential.  A possible alternative might be to perform a strecker degradation on tryptophan to get indole-3-acetaldehyde.  Then add methylamine, reduce, add MeI or MeBr.

That should give you the N,N,N-trimethyltryptammonium salt Shulgin talks about, and a couple of his methods for converting it to what you want are doable OTC.

http://www.erowid.org/library/books_online/tihkal/tihkal06.shtml

via
https://www.hyperlab.info/inv/index.php?act=ST&f=17&t=310&s=f1048bf095a71cc518f66613873f6821

For some reason, I can't edit my post above again.  It wasn't decarboxylating tryptophan that was causing cyclization concern, it was Eschweiler-Clarke methylation of the resulting tryptamine.

The MeI or MeBr methylation will work though, as probably will DMS (or just buffered methanol/H2SO4.)   I'm not sure if DMS would lead to the same trimethyltryptammonium salt, just dimethylate it to what you want, or even do something else funky to it though.

Ausser, do you have a reference for the very last reaction pictured, where 3-indoleacetaldehyde is coupled with dimethylamine?  I didn't realize they could be directly combined that way, which is what I was trying to work out in a round-about way in this thread and trying to work around above.

Alright, so you're just forming the enamine then reducing? Which makes sense, but remember you have to have "water-removing conditions" (dean stark, lots of drying agent, etc.) to push the equilibrium towards enamine formation.  Then the reduction needs to be kept fairly dry too.