This is just theory so far but according to patent EP 0 389 876 N-methyl-3,4-dimethoxyphenylethylamine can be made by the following route:
”3,4-dimethoxybenzaldehyde which, by means of a Darzens condensation, gives an epoxyester that, by alkaline hydrolysis and subsequent decarboxylation, gives the 3,4-dimethoxyphenylacetaldehyde. This aldehyde gives the title amine by reaction with monomethylamine followed by reduction with sodium borohydride.”
There are several interesting aspects in this patent…
Easy reaction from the benzaldehyde to the phenylacetaldehyde
Aqueous imine formation and borohydride reduction
No heating involved at all, just quite mild cooling
76.5% yield of final amine calculated from starting benzaldehyde
I propose, from the theory of this patent, that benzylamine is used instead of monomethylamine and the generated N-benzyl phenylethylamine is converted to the phenylethylamine by hydrogenolysis by either CTH (ammonium formate/Pd-C) or regular low pressure hydrogenation.
Couldn´t also a great number of N-mono or dialkyl tryptamines be made by this route as well, starting from the corresponding indole-3-carboxaldehyde???
Proposed route to 2C-H from 2,5-dimethoxybenzaldehyde:
2,5-dimethoxybenzaldehyde is allowed to react with an alkylester of an alpha-haloacetic acid (eg. 2-butyl chloroacetate) in an alcoholic media at 15-20 deg C, in the presence of a strong base (eg. sodium methoxide) to give an alpha,beta-epoxyester.
This epoxyester gives by alkaline hydrolysis (aq. NaOH or KOH) the alkaline salt of the epoxyacid. Decarboxylation of this epoxyacid salt by acid hydrolysis gives 2,5-dimethoxyphenylacetaldehyde.
2,5-Dimethoxyphenylacetaldehyde is allowed to react with benzylamine and the formed imine is reduced to the amine by aq. Sodium borohydride without isolation. The N-benzyl-2,5-dimethoxyphenylethylamine is isolated and debenzylated by conventional hydrogenolysis.
I´m currently ordering the chemicals needed for some trials. Reports will follow shortly.
