Ketone methylation

[Chemikaze]

Can anyone suggest how to methylate that pretty ketone?

This is Atenolol:



When I die bury me upside down so the world can kiss my ass.

[hypo]

hi,

technically this is not a ketone, it's an amide.
where do you want to methylate it?
official gene trash

[Chemikaze]

Yes, I want to replace that =O group with methyl
then hydrolyse ether linkage and get an amphetamine.

How do we methylate it?

Anyway this Atenolol is cheap (relatively) like shite,and if methylation is not too tedious,then it gonna be cheapest amph (for me)
When I die bury me upside down so the world can kiss my ass.

[PrimoPyro]

Hydrolysis would not reduce the ring to an unsubstituted phenyl group. It would produce a 4-OH phenyl group. Aromatic oxygens are next to impossible to remove "easily" and in good yields. Sorry.  

Or do you know some procedure you'd like to share that does just this?  

[Chemikaze]

That`s what I was thinking about...damn.

But still this is not as important as the question of substituting ketone with methyl,to get our favourite isopropylamine(Ideas?).

And then we always have a choice of methylating that 4-OH,then brominating and methoxylating (we don`t need PMA,right?) ,ending up with smth interesting
If we halogenate it before methylating 4-OH,then halogen would go to 3,5?

Well this isn`t that cheap and easy as I was hoping,but still it looks like a good precursor,doesn`t it?

And the answer to your question - No. I don`t know such a procedure
When I die bury me upside down so the world can kiss my ass.

[Kinetic]

If your intention is to produce amphetamine, you can start with commercially available 2-phenylacetamide, which is the same as above but with the aromatic oxygen already removed. In fact, the N-methyl version is also available (but expensive).

The problem of replacing the carbonyl oxygen with a methyl group is still there though; it's a shame the Wittig reaction only works on aldehydes and ketones. Is there not a modification of this reaction or a similar procedure which allows it to be carried out on amides?

[Chemikaze]

You advise to start from phenylacetamide,how can i start to make it isopropylamine??  
When I die bury me upside down so the world can kiss my ass.

[Chemikaze]

While searching, found an interesting patent
US4761501

This application discloses certain substituted phenylacetamides of the formula: blah...blah...blah.. which are useful in the production of antidepressant agents.

In accordance with this invention there is provided a group of substituted phenethylamine derivatives which are central nervous system antidepressants

Very interesting patent i must admit:)

When I die bury me upside down so the world can kiss my ass.

[Kinetic]

Why do you want isopropylamine? Do you mean phenylisopropylamine (amphetamine)? I suggested 2-phenylacetamide only because it is more closely related to the structure of amphetamine. I had also wondered about making this compound into amphetamine, but couldn't come up with any simple way to add the alpha-methyl group. I had thought of maybe Grignard, but I think Grignards are such strong bases they will still deprotonate the stable nitrogen of the amide. I'd be very pleased if anyone proved me wrong though!

[Tricky]

Khm...
AFAIK, if you'll react your 2-phenylacetamide with CH₃MgBr, finally you'll get P2P, but I think it's very expensive way to amphetamine
There's a hole in our soul that we fill with dope
And we're feeling fine.

[Chemikaze]

That would be a hard way,Tricky,for sure.
Of course i meant phenylisopropylamine...

Elder bees?
When I die bury me upside down so the world can kiss my ass.