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I am trying to devise a synthesis to change synephrine (4-[1-hydroxy-2-(methylamino)ethyl]phenol) into N-methylphenethylamine.

I was figuring that I could remove the hydroxyl group attached to the ethyl part using thionyl chloride to convert the hydroxyl into a chloride and then remove the superior leaving group using $\ce{LiAlH4}$ as a reagent and $\ce{AlCl3}$ as a catalyst, but thionyl chloride affects amine groups and I couldn’t find any information about how to protect the amine group when performing this reaction to reduce the hydroxyl.

I also researched how to remove the hydroxyl from the benzene ring but that involved using zinc and distilling the benzene which wouldn’t work for this because the boiling point of the substance is around 341 °C for synephrine.

Any insight would be really helpful.

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  • $\begingroup$ Can you make an aryl triflate then do Pd-insertion in the presence of a reducing agent like a silane? I dont know if I just made that up or if it’s a thing... $\endgroup$
    – PCK
    Commented Jun 13, 2019 at 19:21
  • $\begingroup$ Yes, you can. Relatively straight forward catalytic transfer hydrogenation Example here sciencedirect.com/science/article/pii/S0040403900852624 $\endgroup$
    – Waylander
    Commented Jun 13, 2019 at 22:27

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Suggested route - step 1 acetylate the amine with 1 eq of acetyl chloride in pyridine.

step 2 hydrogenation of the benzylic alcohol over Pd/C in the presence of acid or use TFA/triethylsilane

step 3 form the triflate of the phenol

step 4 catalytic transfer hydrogenation of the triflate, conditions here

Step 5 acid hydrolysis of the N-acetyl group with cHCl to give product

Thanks to @PCK for the suggestion of forming and reducing the triflate

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