(+/-)-Norephedrin hydrochlorid in the aminorex syn

[Bandil]

Hi!

Swim has a bottle of "(+/-)-Norephedrin hydrochlorid" from acros lying around. For the 4-methylaminorex synth using P. cyanate it calls for the pseudonorephedrine isomer. Do you think swims PPA is a mixture of pseudo and nonpseudo, as swim cannot find the pseudo listed at acros??

Is it useable?

Thanks in advance!

Regards
Bandil

[Bandil]

Just found some more specs on it.

It has the following CAS#: 154-41-6
You can see the product details at:

http://www.sigmaaldrich.com/cgi-bin/hsrun/Distributed/HahtShop/HAHTpage/frmCatalogSearchPost?Brand=ALDRICH&ProdNo=131431

swim would appericiate if you could take a look and give a verdict on swims project!

Thanks!

Regards
Bandil

[Bandil]

Could someone pleeease take a look at the compound and see if its usefull for the cyanate synth? Swim has all the chems ready and just needs a green light from his fellow bees...

[SPISSHAK]

amine is R configuration
The amine steroechemstry is little consequence you want +,- nor-ephedrine.
Pm me for how to isolate that isomer.
Hell I walk you throug it. you can use it to get ~ 50% yeild. and isolate the oxazolidone amide from active product with A/B workup.
I give it a green light!

[Bandil]

According to rhodium, one could use the given PPA in the reaction without the pure isomer and simply isolate the 4-M-aminorex after the reaction with A/B right?

Thanks alot!

Swim will now begin hiw little experiment and of course do a writeup for other bees to enjoy!

Thanks for the help!

Regards
Bandil

[Rhodium]

No, racemic norephedrine would only give the inactive racemic amide using the cyanate route. Norephedrine needs cyanogen bromide to be useful in 4-MAX synthesis.

Edit: I was wrong, see

Post 352258

(Rhodium: "The amide (trans-4-methyl-5-phenyl-oxazolid-2-one)", Methods Discourse)

[bottleneck]

Do you think you could reductively aminate the amide to 4-MAR?

[bottleneck]

Also, why does the amide form from the norephedrine and the proper amine from the pseudo-isomer, while in the article you mentioned in "4-Methylaminorex wo BrCN", it is the pseudo-isomer of ephedrine which gives the amide, and ephedrine gives an imine?

Is this accurate?

[Rhodium]

The amide (trans-4-methyl-5-phenyl-oxazolid-2-one) would not give 4-MAR upon reduction, it would lack a nitrogen atom. It has a double-bonded oxygen where 4-MAR has a double-bonded nitrogen (in one of the resonance forms). You cannot reductively aminate amides.

On the other hand, it seems like you are correct in your critisism of

Post 212038

(Rhodium: "4-Methylaminorex Synth w/o CNBr", Novel Discourse) - it seems like I switched around compound VI and IV when transcribing the information from J Chem Soc, 850-854 (1952), the experimental part of that article is not especially structured, they use ephedrine and pseudoephedrine derivatives alternately, and not simply all the reactions of ephedrine derivatives first, and all pseudoephedrine derivative reactions second.

It seems like the correct reaction table should look like this:

Using the Potassium cyanate route:
Norephedrine -> trans-4-MAR
Norpseudoephedrine -> "Amide"

Using the Cyanogen Bromide route:
Norephedrine -> cis-4-MAR
Norpseudoephedrine -> trans-4-MAR

[bottleneck]

>The amide (trans-4-methyl-5-phenyl-oxazolid-2-one) would not give 4-MAR upon reduction, it would lack a nitrogen atom. It has a double-bonded oxygen where 4-MAR has a double-bonded nitrogen (in one of the resonance forms). You cannot reductively aminate amides.

Okay, I thought you could. Just shows what I know. I just saw the doublebonded oxygen and thought "reductive amination!".

>On the other hand, it seems like you are correct in your critisism of Rhodium: "4-Methylaminorex Synth w/o CNBr" (Novel Discourse) - it seems like I switched around compound VI and IV when transcribing the information from J Chem Soc, 850-854 (1952),

Okay, thank you.

>It seems like the correct reaction table should look like this:

Thanks. I guess it's worth a try with the norephedrine then!

>Do you have the JCS article in electronic format? I'd like to have that, in case it is available.   
 
I don't have it in OCR-form, but I have emailed you the scanned images of the article.