[redcardinal]

I need some help with this problem.

Q. Synthesize 3-methyl-4-phenyl-2-butanone from ethyl acetoacetate

My solution:

1. Use NaNH2, NH3, CH3I to add CH3 to the alpha carbon
2. Use NaNH2, NH3, BrCH2Ph to add PhCH2 to the alpha carbon
3. Use NaOH, H2O, heat to remove COOCH2CH3 group

I am not sure if my solution is correct. Any input?

[discodermolide]

By the alpha carbon you mean the one CH₃ group attached to the C=O of the ketone?
If so which proton is the most acidic in ethyl acetoacetate?

[redcardinal]

By the alpha carbon, I mean the CH2 group in between the carbonyl and ester group.

[orgopete]

The strategy is correct, but the reagents are not. Ammonia will react with acetoacetate to give a beta-aminocrotonate. Check a textbook for other reagents. Step three, as written, will give the carboxylate of the acid, not the desired product.

[redcardinal]

attempt 2

1. Use NaOEt (or should I use a stronger base like LDA with THF?), CH3I to add CH3 to the alpha carbon (CH2 between carbonyl and ester groups)
2. Use NaOEt, BrCH2Ph to add PhCH2 to the alpha carbon
3. Use NaOH, H2O, H3O+, heat to remove COOCH2CH3 group

[AlphaScent]

I am not seeing how you would add benzyl bromide to the methylated methyl acetoacetate...

Is it 3-methyl-3-phenyl-2-butanone you mean to make??

[redcardinal]

I was thinking that there is still another alpha hydrogen on the CH2 carbon between the carbonyl group and the ester group so I could replace the hydrogen with the benzyl bromide.

Yes, I am trying to make the desired product, as shown in the figure attached.

I am confused (beginner at organic chem)...what would be the alternative to step 2 if benzyl bromide won't work?

[AlphaScent]

Ok, I see what you mean now.  I was wrong.  Yes that will work. 

The decarboxylation is the tricky part. You may have to isolate and then heat the acid to remove CO2.

When you perform the saponification you may result with the sodium salt of the acid.

[redcardinal]

Thanks!

Is there another way of achieving the same results? For the organic chemistry experts - how would you go about solving the problem?

[orgopete]

The modified scheme is fine. An alternate method could use aqueous acid to hydrolyze and de carboxylate the ester. In the lab, NaOH is a reliable hydrolysis though.