chemrox
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4-Amino-1-phenethylpiperidine | CAS: 51448-56-7
I plan to make the desired intermediate by dissolving the N-phenethyl-4-pieridone from an earlier synthesis in ethanol and adding hydroxylamine HCl in
water to the mixture. After refluxing the above for an hour needles of the oxime should pcpt. Reducion with Na/ethanol should yield the desired amino
piperidine. This is after Lindwall and Harper & Chignell, '64.
Attachment: The Chemistry and Pharmacology of Some 4-Aminopiperidines and Their Derivatives.pdf (506kB)
This file has been downloaded 820 times
"When you let the dumbasses vote you end up with populism followed by autocracy and getting back is a bitch." Plato (sort of)
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prettypolymer
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Would you like some propionic anhydride along with that, my good sir?
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solo
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" Would you like some propionic anhydride along with that, my good sir? "......prettypolymer
.......? when all you need is aniline and a reduction and Propionyl Chloride......as a theoretical synthesis ...solo
It's better to die on your feet, than live on your knees....Emiliano Zapata.
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chemrox
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No thanks and Solo is correct if you want to make the propionamide.. I don't. Not for this one. Nor aniline thank you Solo.. different compound..
another route.
"When you let the dumbasses vote you end up with populism followed by autocracy and getting back is a bitch." Plato (sort of)
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clearly_not_atara
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This is one of those syntheses that worries me because it might really kill the person who tries it. Anyway you might be able to do it by making
4-aminopyridine from 4-pyridylpyridinium as in the preparation of 4-DMAP.
http://en.wikipedia.org/wiki/4-dimethylaminopyridine#Prepara...
Protecting the amine terminus, 1-alkylation with phenethyl bromide, and hydrogenation gives the target compound. Please be safe and don't make any
chemical weapons.
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solo
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......a very nice approach Atara,....say bye to the 4-piperidone and all the acrylates .......solo
It's better to die on your feet, than live on your knees....Emiliano Zapata.
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chemrox
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Thanks for the info. Since I already have N-phenethyl-4-piperidone I probably won't go this route but I'm interested as an alternative for making
N-phenethyl-4-piperidine. I don't generally like working with Cl2 and couldn't find any details on the first step. Do you have a ref for that?
Anyway was looking for comments on the hydrazine reaction and conditions. I know the NPP would dissolve in alcohol and was also thinking of running it
in MeOH with reduction using EtOH (denatured)/Na
Or maybe do the reduction with MeOH/Na and avoid any issues with EtOAc in the mix. (I'm really short on anhydrous undenatured EtOH)
[Edited on 16-3-2016 by chemrox]
"When you let the dumbasses vote you end up with populism followed by autocracy and getting back is a bitch." Plato (sort of)
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CuReUS
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but isn't it wasteful, one mole of product in exchange of 3 moles of reagent
do you mean N-phenethyl-4-aminopiperidine ? In that case I have some ideas
1. from phenethylamine and divinylketone :
read the 19th post of nicodem in this thread
http://chemistry.mdma.ch/hiveboard/newbee/000480940.html
reduce the piperidone to amine using leukart reaction http://cccc.uochb.cas.cz/55/5/1297/ pg 1305
| Quote: | A mixture of 11·4 g I-benzyl-4-piperidone, 40'5 g formamide, and 8'5 g formic acid was stirred for 30 min at l00-125°C and 5 h at 170°C(bath
temperature 190°C). It was evaporated under reduced pressure (bath temperature until 145°C), the residue was dissolved in 70 ml benzene, the
solution was washed with water, IM-NaOH, and water, dried, and evaporated; 9'6 g (73%) 'of crude l-benzyl-4-(formamido)piperidine. It did crystalline
neither in the form of the base, nor
as the oxalate. The crude intermediate (6'7 g) was disolved in 15 ml ethanol, 14 g KOH were added and the mixture was stirred and refluxed for 4 h.
After cooling the mixture was diluted with 50 ml water and extracted with ether. Processing of the extract gave 5·7 g (97%) of crude
4-amino-I-benzylpiperidine which was distilled, b.p. 93-95°cj40 Pa. Ref. 17 , b.p. 113-116°C/80 Pa (different method). |
you can also reduce the oxime using LiAlH4
http://pubs.acs.org/doi/abs/10.1021/jm00123a028
in this paper they also mention that the diamine(4-amino phenethylpiperidine) is sensitive to air oxidation,so keep that in mind
2. from isonicotinic acid :
similar to atara's method,isonicotinic acid is reacted with phenethylbromide,hydrogenated and finally a schmidt reaction is done to get
4-aminophenethylpiperidine.In case there is a chance of the phenethylbromide reacting with the COOH to form an ester(which I doubt),then
isonicotinamide has to used which can be converted to the amine using bleach
| Quote: | | I don't generally like working with Cl2 |
I think TCCA or bleach can be used instead of Cl2 but I may be wrong
| Quote: | Anyway was looking for comments on the hydrazine reaction and conditions. I know the NPP would dissolve in alcohol and was also thinking of running it
in MeOH with reduction using EtOH (denatured)/Na
Or maybe do the reduction with MeOH/Na and avoid any issues with EtOAc in the mix. (I'm really short on anhydrous undenatured EtOH)
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http://cccc.uochb.cas.cz/55/5/1297/
on pg 1299,they talk about hydrazine hydrate reduction.I didn't read it so go through it if interested
on pg 1298,they talk about Na/ethanol reduction
| Quote: | | 4-amino-l-benzylpiperidine has been prepared not only by the methods described (reduction of I-benzyl-4-piperidone oxime(22) with sodium and
ethano1(23) or with lithium aluminium hydride 16 ,17) but also by making use of the Leuckart reaction(24) |
[Edited on 18-3-2016 by CuReUS]
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zed
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Some have suggested the oxime may be reduced via Aluminum Amalgam.
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skip
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Chemrox,Have you experience with sodium in etOH ? I tried it one time with pyridine and failed. I believe algamated sodium in etOH is what really
works. I no longer care about piperidine. The point I wanted to make was that the whole time I was adding sodium I was a nervous wreck , scared that
the anhydrous etOH wasn't dry. The sodium was cut into pea size chunks and it was skimming on top and etOH was boiling like hell. I would add a small
chunk and get away until it was about gone, the whole time I thought it was going to turn into a fire ball. If you have done it then I appoligize.
Honestly I think the sodium in etOH cited in literature is bull, I may be wrong.
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spankyetal
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PEA-4-piperidone etc
the newer reactions involving the tried and true amine/acrylate additions and subsequent Dieckmann cyclization with Na sand in toluene have major
improvements. One pot reactions with 91% yields of the target biesters and 58%+ yields of the 2-PE- 4-piperidone and beyond are very impressive.
Nanosulfuric acid catalyst without any solvent is awesome. No microwaves either. Having hands-on experience I can relate the literature on Dieckmann
cyclizations leads to failure or dismal yields. Major critical details are left out of the older literature as the authors ASSUME the readers are up
on a-prior-art. Like using a Helium cloud instead of N2. Alkaline pyrogallol scrubbing of O2 from that cloud. etc. Producing Na sand and accurately
weighing it. etc.
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spankyetal
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PEA-4-piperidone etc
Na sand can easily be made by rapidly stirring molten sodium in toluene just above the melting point of Na and then cooling the mixture to keep the
sand in particle form. The faster the stirrer the smaller and more effective is the sodium sand in the next cyclization Rx. The sand is made alone and
not in situ during the cyclization rx. It will stay in particle form as the reaction is maintained at 80 C or so and sodium doesn't melt until 97 C.
[Edited on 7/24/2017 by spankyetal]
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spankyetal
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these analogs did injure aa significant number of people in central california. DOJ labs traced it back to imperfect hydrogenation step yielding
severe neurotoxins. carefull what ya wish for
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