[sanaldev]

im doing  masters degree in medicinal chemistry..plz tell me a method to hydrolyze ketorolac tromethamol.its a Nonsterodial anti inflammatory drug ..i have to seperate ketorolac  from this tromethamol salt form.

i have done the following.. since ketrolac  tromethamine is soluble in water i dissolved it in water and made the  PH 4 using HCl  and stirried for 5 hrs then  its extracted with chloroform and monitored the  TLC  of the chloroform extract ..but i didnt observed much diffenence ..i isolated the same compud and checked the melting point but its  same as that of ketorolac tromethamol..plz give me an method to  seperate ketorolac from its salt

[Nucleophile]

First, is this the culprit?:


Second:
What's your precise goal? to separate it? I am sorry if this sounds stupid, but have you tried various chromatographic methods? what did a TLC of the original material dissolved in say DCM show?

[movies]

You might try dissolving the sample in some CH₂Cl₂ and washing with aqueous CuSO₄ solution.  That is supposed to be good for removing Lewis basic things.  You might end up pulling out the acid too though.

[sanaldev]

my  aim is to seperate  ketorolac troimethamol  to pure  ketorolac ie... free from tromethamol salt. i want to couple it with cyclodextrin using DCC coupling. its there in the literatrure that after the administration  of  ketorolac tromethamol (salt form) get hydrolyzed to liberate the free  ketorolac  at Physiological pH (ie..7.4) and its gets absorbed into the systemic circulation ..can i  try  hydrolyzing at pH 7.4 ? will it work? give me your suggestions?

[Dude]

     I don't see any organic moieties that would undergo an irreversible reaction in moderate acid or base solution.  
     I would first try a much lower pH than 4 to get the "ketorolac" material to precipitate.  Dissolve the salt in a minimum of distilled water and then add it to a large excess of 10 % HCl.  Acid/base reactions are generally immediate so don't waste 5 hours stirring - give it about 5 minutes.  If you don't see a precipitate, then try a methylene chloride wash to obtain the free acid.  If that still doesn't work, I would add base to the salt (i.e. 10 % sodium hydroxide) and then add it to a large excess of acid and try the same approach.

[sanaldev]

thankyou .

[Nucleophile]

Everyone:
The ketrolac has an amine group too, and I feer that in acidic conditions it still will be mostly water soluble, because now the amine will be protonated.


How about Reverse-phase chromatography?

[movies]

Everyone:
The ketrolac has an amine group too, and I feer that in acidic conditions it still will be mostly water soluble, because now the amine will be protonated.


How about Reverse-phase chromatography?

Reverse-phase is a great idea.

The amine in ketrolac isn't nearly as basic as a regular amine  because the electrons are involved in the aromaticity of the pyrrole.  The pK_a of protonated pyrrole is -3.8 (about as strong an acid as a protonated ether).  By the way, it protonates on carbon, not nitrogen.

[sanaldev]

hi everyone..

   I extent my heartfelt thanks for your valuable suggestions..
   respected sir as suggested by you our first approach was to separate the salt by RP-HPLC but our research lab doesn't have the sophisticated column to separate it in preparative level.

 sir, so i do expect any valuable suggestions that are into my reach for my further proceedings for the synthesis part.

waitning for your kind suggestions..



   

[Nucleophile]

Reverse-phase is a great idea.

The amine in ketrolac isn't nearly as basic as a regular amine  because the electrons are involved in the aromaticity of the pyrrole.  The pKa of protonated pyrrole is -3.8 (about as strong an acid as a protonated ether).  By the way, it protonates on carbon, not nitrogen.

D-oh! You're of course right about the pyrrole - the lone pair is involved in the ring aromaticity. For some reason I've missed the pyrrole in the stucture altogether, thinking it for simply a vynilic amine to a conjugated diene ( i.e I thought that the other end of the pi system isn't next to the amine.)

Sorry for my mistake.