[karlyip]

Dear All,

I am in trouble in my research as my supervisor asked me to synthesis a thiol functioned cephalosporin , then I coupled a S-trityl protected mercaptoacetic acid with the amine group of the C6 position in the 7-ACMA. As the figure shown:

2 by karl_ycy, on Flickr

I am trying to deprotect the S-trityl group to give thiol, is it possible to remove the trityl group by using TFA and triisoopropylsilane? Or any alternative? Also, since beta-lactam is quite a sensitive compound, should I perform the deprotection in ice bath?

Thanks for your attention! 

[discodermolide]

Dear All,

I am in trouble in my research as my supervisor asked me to synthesis a thiol functioned cephalosporin , then I coupled a S-trityl protected mercaptoacetic acid with the amine group of the C6 position in the 7-ACMA. As the figure shown:

2 by karl_ycy, on Flickr

I am trying to deprotect the S-trityl group to give thiol, is it possible to remove the trityl group by using TFA and triisoopropylsilane? Or any alternative? Also, since beta-lactam is quite a sensitive compound, should I perform the deprotection in ice bath?

Thanks for your attention! 

Try TFA/DCM 1:1 in water at 0°C to RT. I think the beta-lactam will survive.

[karlyip]

Dear All,

I am in trouble in my research as my supervisor asked me to synthesis a thiol functioned cephalosporin , then I coupled a S-trityl protected mercaptoacetic acid with the amine group of the C6 position in the 7-ACMA. As the figure shown:

2 by karl_ycy, on Flickr

I am trying to deprotect the S-trityl group to give thiol, is it possible to remove the trityl group by using TFA and triisoopropylsilane? Or any alternative? Also, since beta-lactam is quite a sensitive compound, should I perform the deprotection in ice bath?

Thanks for your attention! 

Try TFA/DCM 1:1 in water at 0°C to RT. I think the beta-lactam will survive.

discodermolide, Thanks for your reply!

I tried and after I removed all the solvent, a brown oil obtained. May I ask how can I purified the product? The deprotected product is very soluble in water (its log P is around -0.6)

[discodermolide]

Well you could try and crystallize it. Or run it through a flash column.

[karlyip]

What a painstaking process...

I deprotected the beta-lactam, however I can't obtain the product
I have tried to precipitate it by cool ether, but it just like some gel and stick on the filter paper as it is in very small amount (0.060mmol scale) so that I can't recover the product from the filter paper...

What can I do... 

BTW, thanks for your attention.

[discodermolide]

What a painstaking process...

I deprotected the beta-lactam, however I can't obtain the product
I have tried to precipitate it by cool ether, but it just like some gel and stick on the filter paper as it is in very small amount (0.060mmol scale) so that I can't recover the product from the filter paper...

What can I do... 

BTW, thanks for your attention.

Don't use ether, it tends to make things hydroscopic! Try a higher boiling ether like diisopropyl ether.
Redissolve the product in CH2Cl2, then remove the solvent and put the residue under high vacuum to remove the last of the TFA.
Is the ring still intact (IR?)

[Babcock_Hall]

discodermolide,

We have a similar situation (possibly the subject of a future thread).  What about using MTBE as the ether versus diisopropylether?  Thanks.

[discodermolide]

discodermolide,

We have a similar situation (possibly the subject of a future thread).  What about using MTBE as the ether versus diisopropylether?  Thanks.

MTBE also tends to make the compounds hydroscopic but not as bad as ether. I found that using ether after an acid hydrolysis the compound was impossible to isolate. I changed ethers (experimentation) but more importantly made sure all traces of acid were removed, usually by rotavaping in water or water/toluene several times followed by a several toluene azeotropes.