Theory:
When the initial norephedrine hydrochloride is mixed with potassion cyanate, it forms the carbamoyl compound in near quantitatie yeilds with respect to the norephedrine. The original patent's uses a slight molar excess of the cyanate in order to give complete conversion. When the first reaction is done, there should thus be a mixture of: N-carbamoyl-norephedrine, potassiumchloride and traces of of cyanate. The remaining cyanate will be destroyed by the huge excess of acid which will be added later. In the end these impurities should have no influence of the ring formation, catalysed by the acid. It should in theory be possible to do the initial reaction and simply add the acid in one portion while heating continusouly till the reaction is over. With this in mind, it seems kind of a waste to isolate the intermediate, so this has to be tested 

Practicein theory of course)
5 grammes of norephedrine.HCl(26,5 mmoles), was placed in a 100 mL FBF, and 2,3 grammes of KOCN(28,4 mmoles) and 25 mL's of distilled water was immediately added in succession. This was heated to reflux directly on the hotplate for two hours. 

After this time, 30 mL's of 2M HCl(60 mmoles) was added. This caused a bit of bubbling(probably from the excess cyanate being broken down to gasseus -i-cant-remember-what-). Reflux was continued for an additional two hours. The mixture took on an ever so slight pinkish tint, which the "old" synth also tend to do at this stage.

After 2½ hours of reflux, the mixture was cooled and basified with sodium carbonate and presto a lot of pretty white crystals precipitated on the bottom of the beaker. The yeild looked like that which is expected from the normal reaction. They will be measured shortly.

Conclusion
Total success!!
We'll the usual cyanate route to 4-methylaminorex was easy, but this is more like baking a shake-n-bake cake really (which is VERY easy if you didn't know). Bioassay's are pending though, but nothing that was put into the flask would have reacted the way, the final product did. The yeild will also be measured shortly!

Have a nice and productive weekend!

Kind Regards
Bandil 



More info from Bandil...


Since the last 4-methylaminorex postings, further improvements to the
shake'n'bake method has been discovered. The final missing milestone in
the synthesis was the lack of a decent salting procedure. None of the
methods originally devised by Eleusis / Zwitterion actually worked for
making the salt. Several bees have tried the method and all failed.

The only way of making a salt is by adding equimolar amounts of
hydrochloric acid, adding 10X xylol and azeotropically distilling the
water / xylol away. Xylol binds water to a greater extent than toluene,
which makes it more suitable for drying stuff. After the solvent has been
stripped, some acetone is added and the whole mess cooled in the freezer.
This will leave glister white crystals of the hydrochloride in near
quantitative yields.


L-alanine/benzeldehyde condensation = norpseudoephedrine <-- [boil in hcl acid for 4 hours to get 50% yeild of the desired norephedrine]

urea/sodium bicarbinate condensation = sodium cyanate

norephedrine/sodium cyanate---->U4EUA