Generally speaking, acetamides are rather difficult to hydrolyze. Try NaBH4, THF, H2O, 0C to r.t. though you might reduce the ketone to the alcohol...

Also NH3, MeOH, in acetonitrile

You could try out suitable enzymes like acylases (hog kidney, aspergillis) which work under mild conditions.

In case you have an NHAc you might be able to introduce a Boc (Boc2O, DMAP, DCM). Then the Ac can be cleaved in very mild conditions (eg LiOH, THF/H2O 8:2, RT). Subsequently the Boc could be cleaved either at RT using HCl in ether or heating in neutral conditions (eg uw @150C, 15min).

Dear Pascal, Thanks for suggestion

Can you send me the research article related to this type of work

I also wanted to try enzymes like acylasesenzymes like acylases but they are quite costly.

Dear Yekaterina,

Will NH3 work for my compound? Are you sure about it. Please let me know

Thanks

if its only an amide ,it can be hydrolyzed by either 40 % aq. NaOH or 70 % H2SO4; the only care to be taken is you should neutralize the resultant solution appropriately to recover the product.

NO problem it is easy.6N HCl 5vol and your compound.

reflux for 6hrs.block colour reaction will come.

wash the reaction mass with DIIsopropyl ether 5 times.

distill out water completely.then isolate in acetone.

Dear Yellanki,

I tried it till Conc. HCl but the reaction did not proceed as I wanted.

Dear Omprakash,

Try with HCl in dioxane. I have done it using dichloromethane as solvemt. Conditions: RT for 20hr, under nitrogen atm, Ammonium chloride salt formed is separated, dissolved in water, neutralised by Sod.bicabonation solution followed by extraction. Yield was app. 50%.

use sodium hydroxide in methanol and refluxe for 3 hr

Now that I think about it, the NH3 in methanol works for aziridines (increased rate of hydrolysis since the nonplanar amide moiety cannot participate as wel in the resonance of the amide). However, do try the 85% hydrazine, ~70C, or the hog kidney acylase, pH7, water, 36C (may take a long time, ~overnight), and/or the conversion to the BOC group approach. If you would like articles for each ne, please let me know.

A teacher friend of mine told me to tell you to use Potassium hidroxide concentrated with some heating.....

Dear Sheela,

Have you done this type of amide hydrolytic reaction in which there is a beta-keto group near acetaamide. group.

Sorry Mr. Omprakash,

I have done on furan moiety with amide( acetamide) group in 3-position.

For synthesis of drugs see www.drugsyn.org

If there is no other reducable group then try reduction using NaBH4 or add grignard reagent that would react with acetyl group.

This could be a very difficult hydrolysis. It would seem that under basic conditions, elimination would be a problem (to give a styrene) which could potentially then go on to other products. Similarly, under acidic conditions, one could promote condensation reactions and possibly eliminations as well. One of the interesting suggestions below involved using hydrazine, but I think in this case one would most likely obtain a the double condensation product. The N-Boc derivative might work if sufficiently mild conditions could be found to hydrolyze the imide, but again, elimination is a risk. This might be a case where installing the N would best be done via a 1,4 addition (azide or something else that can be reduced without touching your ketone). Good luck!

See our site for protecteurs groups, (for amide page 18) http://www.biocis.u-psud.fr/IMG/pdf/Gpts_protecteurs.pdf

2 new methods to try

1) Tf2O, then imine cleavage...

2) Triphenylphosphite.Cl2, then imine cleavage, O.L, 2004, page no. around 3700-4000

Dear Conard,

Will this work for my system, Do you have any article related to that, if you have please send it to me at [email protected]

Hydrolysis with the H2o

Are you sure Ramkumar

You can go for the acid hydrolysis.

Dear Omprakash, I apologize of my late answer. Here are the papers concerning a deprotection of the acetyl group:

1. Bocylation: Tet Lett, 50(50), 6977-6980; 2009

2. Acetyl removal: JACS, 125(44), 13486-13489; 2003

3. Boc cleavage: classical way with HCl in ether, DCM, RT, 12h

I hope it will work in your case.

Dear Pascal,

Are you sure that for Acetyl removal: JACS, 125(44), 13486-13489; 2003 is the reference.

I could not find any thing like that.

Please help

thanks

Base catalysed hydrolysis is the best one.

Dear Omprakash, please check in the supplementary material on the step for the synthesis of compound 4. The acetyl deprotection is described on top of page S21 by using K2CO3, in MeOH.

For methods closer to your case, you could check the following references:

. H2NCH2CH2NEt2, MeOH or MeCN

-> Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, B41(1), 18-23; 1987

. Hydrazine, MeOH or MeCN: Journal of the Chemical Society, Chemical Communications, (19), 1317-18; 1985

I hope it will help you.

Dear Pascal,

Thanks for help. I saw the articles but I could not access them, if possible can you send me a copy of these articles. Because it seems that they might have done the same work as mine,

Please help.

Thanks

Dear Omprakash, I will try to get them, but it will not be easy.

At first, I would try to protect the carbonyl function using acetalation (e.g. formation of dimethyl ketal), then the basic hydrolysis of acetamido group (e.g. barium hydroxide in water) and finally, deprotection using hydrolysis in mild acidic conditions.

Sergey, what do you want to say? can you explain it with drawing. Thanks

If I understand your situation correctly, the carbonyl function ensures lability of your compound in basic or acidic media. In that case you need to protect this function and then perform hydrolysis of the amide group.

Sergey, you are right, you got it right. I just want to know that do you have exact procedure for the steps you have mentioned. If you have please let me know.

Thanks

I can look for corresponding experimental procedures in literature if you want. It takes some time.

Do the base hydrolysis with the weak bases to avoid the problem you have faced with NaOH hydrolysis. B'cos there is no other best method than this even though with the low yields

You can try with hydrolysis in presence of KOH or K2CO3 or 1mM NaHSO3 and use 0.1N HCl so that I think you will not face the degradation problem in MeOH (Polar) solvent which will induce the formation of amines

or else

You can try the same HCl and NaOH hydrolysis with 0 deg which would reduce the heat liberated which would have caused degradation problem in your case.

I would suggest NH3/MeOH (bubbling NH3 for few minutes in MeOH, then add the starting material dissolved in MeOH)

i think this will help you

http://books.google.co.in/books?id=QSQREqF-TAwC&printsec=frontcover&dq=inauthor:%22Stuart+Warren%22&hl=en&sa=X&ei=kY6aUK2DLJDJrAec24CoDA&ved=0CDcQ6AEwAA#v=onepage&q&f=false

Acid and basic hydrolysis work, but the result dependes on the nature of your molecule. If yoiu have trouble with acetyl group, change to trifluoroacetyl which is more easily removed under mild basic conditions.

Read Greene-Wuts's "Protecting groups". There methods of protecting and deprotecting of different functional groups are described.