Theory: When the initial norephedrine hydrochloride is mixed with potassion cyanate, it forms the carbamoyl compound in near

quantitatie yeilds with respect to the nore phedrine. The original patent's uses a slight molar excess of the cyanate in ord er to give complete conversion. When the first reaction is done, there should th us 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 whi ch 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 conti nusouly till the reaction is over. With this in mind, it seems kind of a waste t o 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 adde d in succession. This was heated to reflux directly on the hotplate for two hour s. After this time, 30 mL's of 2M HCl(60 mmoles) was added. This caused a bit of bu bbling(probably from the excess cyanate being broken down to gasseus -i-cant-rem ember-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 thi s stage. After 2 hours of reflux, the mixture was cooled and basified with sodium carbonat e and presto a lot of pretty white crystals precipitated on the bottom of the be aker. The yeild looked like that which is expected from the normal reaction. The y will be measured shortly. Conclusion Total success!! We'll the usual cyanate route to 4-methylaminorex was easy, but this is more lik e baking a shake-n-bake cake really (which is VERY easy if you didn't know). Bio assay's are pending though, but nothing that was put into the flask would have r eacted 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 f or 4 hours to get 50% yeild of the desired norephedrine] urea/sodium bicarbinate condensation = sodium cyanate norephedrine/sodium cyanate---->U4EUA