[Chudasama]

I just wondered whether it was possible to react an alcohol with allyl bromide when i already have an N-acetyl amide present in my starting (alcohol containing) molecule...

I am really very puzzled as i have never come across a problem like this before...i know i can hydrolyse the amide to an amine, Cbz protect the amine and do the reaction on the alcohol, then cleave the protecting group and N-acylate but is this all necessary?

Also would i need to intially deprotonate the alcohol in order to get it to react with allyl bromide, or is allyl bromide a strong enough electrophile such that i only need a weak base to remove the proton after O-alkylation (i.e. is something like NaH really needed? and if so...wouldn't this deprotonate the amide also and bring about the formation of mixtures even if 1 equiv. was used owing to their similar pKa's)

If anyone can help it would be much appreciated

[agrobert]

First of all what type of alcohol is it? 1º , 2º, or 3º? What about your amide?  You probably need a strong base like NaH to deprotonate your alcohol but you make have some selectivity.  You need to try your reaction on a small scale.  A BOC or CBZ amine would certainly be less reactive, but try your amide first to see if you can skip two unnecessary steps.

[Chudasama]

Thanks for your reply

It's a primary alcohol and a secondary amide...i thought about using 1 equiv. of LDA instead of NaH seeing as it so bulky...do you think this would work?

[agrobert]

Either way is worth a try.  You will inevitably get some deprotonation of your amide but the negative charge will be delocalized within the acyl group.  The primary alkoxide is a prime nucleophile for displacement of your bromide.  Depending on solubility DMF or THF can be great solvents for this reaction.  It may require some tinkering, perhaps slight excess of NaH to deprotonate the alcohol quantitatively and concentration of reaction is always important.

Good luck.

[Chudasama]

Cheers mate

Will give LDA a try first...