Rhodium ...After reading https://www.thevespiary.org/rhodium/Rhodium/chemistry/amphetamine.methylation.html (https://www.thevespiary.org/rhodium/Rhodium/chemistry/amphetamine.methylation.html)
, which did not show in my search for methylating amino groups, I see what you mean as to the successive methylation as you stated. The article is directed to the treatment of amphetamines so would this also work for phenylalanine ?
As to the reactions that are parallel to the reduction of the COOH once the amine group has been methylated , as with the method stated above, how about the Phosphorous /Iodine environment in the reduction of the OH in ephedrine, Pseudoephedrine? I also didn't imply that the reaction differentiated between on or the other, that you read into the question.....java
Addendum; I especially liked the one with formaldehyde, I wonder if the amino acid will be soluble in this solvent to form the formaldehyde imine in a reflux? then hydrogenate with Pt. to reduce to the desired methylated amine.
Here is a prep of N-methyl-phenylalanine, N-methyl-alanine and other N-methylated amino acids. As the intermediate product is the N-Benzyl-N-methyl-amino acid, you have your protecting group attached which you can use to prevent side-reactions on the nitrogen. When you have reduced the carboxylic acid to a methyl group via the intermediate halide you can then remove the benzyl group with Zinc/Ammonium Formate as described in Post 512088 (https://www.thevespiary.org/talk/index.php?topic=11698.msg51208800#msg51208800)
(Rhodium: "Zinc/Formate: CTH Debenzylation (N-/O-/S-)", Novel Discourse)
Die Synthese optisch aktiver N-Monomethyl-Aminosäuren
P. Quitt, J. Hellerbach und K. Vogler
Helv. Chim. Acta 46, 327-333 (1963) (https://www.thevespiary.org/rhodium/Rhodium/pdf/n-methyl-amino.acids.pdf)
(https://www.thevespiary.org/rhodium/Rhodium/pdf/n-methyl-amino.acids.pdf)
Abstract
A synthesis of optically active N-monomethylated amino acids (V) is described. It involves a three-step process, starting from optically active amino acids (I) which are converted into their benzyl derivatives (III), subsequently methylated (IV) and finally hydrogenolyzed. The reaction sequence proceeds without racemization.
This is a post that compliments this inquiry....thanks to Rhodium bringing it to my
attention......java
Post 524301 (https://www.thevespiary.org/talk/index.php?topic=12124.msg52430100#msg52430100)
(Rhodium: "NaBH(OAc)3 Reductive Alkylation of Amino Acids", Novel Discourse)