[anna.kolinski]

I am trying to add a Me group to the amine in the compound attached.

To do this my plan was to add methanol - however I don't want the carboxylic acid to react.
 
I was going to use a benzyl ester protecting group on the carboxylic acid, but will this protect the amine too?

Or any other ideas?

Thanks

[Babcock_Hall]

One thing I noticed was a lack of particulars in your question.  How would you react benzyl alcohol, and how will you react methanol?  Will your ketone need to be protected?  Some general thoughts:  I suspect that you can make a benzyl ester without a reaction at nitrogen.  However, I cannot see an obvious way to methylate a nitrogen using methanol (I could be missing something), and that is why your reaction conditions may be important.  I will let the organic specialists (which I am not) weigh in with more detailed answers.

[k1mng]

Hi anna. As Babcock_Hall mentions, there is a lack of detail in how you'll go about with your transformation. I think this is also a matter of strategy and choosing which transformations to attempt first.

Methanol with some auxiliary acid/base will definitely not methylate an amine and you'd likely only get esterification with those conditions.That being said, you'd be able to esterify your carboxylic acid with benzyl alcohol easily without methylating the carboxyl group first.

Perhaps also think about what other reagents could yield a methyl equivalent for reaction with the nucleophilic amine, as methanol is a poor electrophile. Also, carboxylates/carboxylic acids are very poor nucleophiles so you'd find that by selecting the right electrophiles you could avoid reaction at the carboxylic acid - that is if you decide to do the methylation prior to esterification.

[kriggy]

Why not use lets say methyl iodide? You might get some estser but you could hydrolyze it easily as a part of workup

[Dan]

Why not use lets say methyl iodide? You might get some estser but you could hydrolyze it easily as a part of workup

The textbook problem with that is further reaction of the tertiary amine with MeI to give the tetraalkylammonium salt. It might work out fine in real life though.

There are of course other, more chemoselective ways to do it. Anna, what reactions of amines do you know?

[anna.kolinski]

Thanks for your help, I know imine formations and reactions with electrophiles - how about the Eschweiler Clarke reaction using formaldehyde to form an imine and then formic acid to give the methylated amine?

[kriggy]

The textbook problem with that is further reaction of the tertiary amine with MeI to give the tetraalkylammonium salt. It might work out fine in real life though.

Yea, youre right. after some more classes after ochem 2 im used to "it depends on conditions"

Thanks for your help, I know imine formations and reactions with electrophiles - how about the Eschweiler Clarke reaction using formaldehyde to form an imine and then formic acid to give the methylated amine?

That could work just fine 

[Dan]

Thanks for your help, I know imine formations and reactions with electrophiles - how about the Eschweiler Clarke reaction using formaldehyde to form an imine and then formic acid to give the methylated amine?

Yes, reductive amination of formaldehyde would be my choice of reaction as well. You could also use formaldehyde, H₂, Pd/C and other variations.

[clarkstill]

I'd go Eschweiler-Clarke.

http://en.wikipedia.org/wiki/Eschweiler%E2%80%93Clarke_reaction