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And if you have the correct stereoisomer of methcathione should be able to do the reduction to d-methamphetamine directly, without preparing the (pseudo)ephedrine first. This should also benefit overall yields.
Nevertheless the best way would be in my eyes to go with BMK -> P2P - reductive amination with (S)-(−)-α-Methylbenzylamine and NaBH4 -> d-N-benzylamphetamine -> debenzylation and monomethylation one pot with Pd/C and paraformaldehyde, done as CTH style reaction with formate salts as hydrogen donors -> d-methamphetamine.
The drawbck being the high costs of Pd/C, but still worth it regarding the value of the product.
Nevertheless the best way would be in my eyes to go with BMK -> P2P - reductive amination with (S)-(−)-α-Methylbenzylamine and NaBH4 -> d-N-benzylamphetamine -> debenzylation and monomethylation one pot with Pd/C and paraformaldehyde, done as CTH style reaction with formate salts as hydrogen donors -> d-methamphetamine.
The drawbck being the high costs of Pd/C, but still worth it regarding the value of the product.
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Directly?
Until I know should be like this:
Propiophenone->2-Bromopropiophenone->Ephedrone->d-ephedrone->d-Secondary amine->d-Meth.
Right?
Until I know should be like this:
Propiophenone->2-Bromopropiophenone->Ephedrone->d-ephedrone->d-Secondary amine->d-Meth.
Right?
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In this case there is no problem, you can reduce Methcathione aka Ephedrone to Meth directly, no need to make ephedrine first. And if the ephedrone is the right stereo isomer you will get d-Meth
Propiophenone->2-Bromopropiophenone->Ephedrone->chiral resolution followed by H3PO2/I reduction->d-Meth.
Propiophenone->2-Bromopropiophenone->Ephedrone->chiral resolution followed by H3PO2/I reduction->d-Meth.
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I just realized that Ephedrone is prone to the keto–enol tautomerism and will probably racemize in solution. This sounds bad but actually you might have stumbled here on something really neat. As you can still get the d-isomere to crystallize out of solution as when not dissolved the racemization won't happen. And with d-isomere crystallized out you can use Viedma ripening or a similar technique and you end up with 100% d-ephedrone salt.
And you can throw this salt in portions directly into the H3PO3/I reaction where it gets instantly reduced to d-Meth with no time to racemize, the strongly acidic conditions will help to prevent it too. Means you will not loose any of your product by separating the d-, all will be turned into d-.
And no this does not work for Meth or Amph, this only works for compounds which racemize by themselves or can be made to racemize by adding something (a ultra-strong base or so) to the solution.
And you can throw this salt in portions directly into the H3PO3/I reaction where it gets instantly reduced to d-Meth with no time to racemize, the strongly acidic conditions will help to prevent it too. Means you will not loose any of your product by separating the d-, all will be turned into d-.
And no this does not work for Meth or Amph, this only works for compounds which racemize by themselves or can be made to racemize by adding something (a ultra-strong base or so) to the solution.
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So in that case to have the d-ephedrone in the solid part I must use l-tartaric and I guess it was a typo mistake but would be H3PO2/I reduction.
Thanks a lot for your help.
Thanks a lot for your help.