After deprotection of the tert-butyl ester to generate the carboxylic acid in chloroform with TFA, my compound‘s pyridine moiety forms a TFacetate ammonium salt (small molecule drug, not a peptide; although: 1 amide bond). What would you recommend to either -preferably- generate the ‚free‘ zwitterion or to generate the HCl salt. Will diluting in 1M HCl suffice to protonate the TFacetate to evaporate it off and be left with the HCl salt?
Thanks!
Evaporation with aqueous HCl (1 M or so) followed by evaporation w/water should give you the desired hydrochloride. Alternatively, you may apply your compound on a column packed with a strong cation exchanger and remove trifluoroacetic acid by washing the column with 3 volumes of water. The compound should then be eluted with a volatile base e.c. 4% aq. triethylamine followed by evaporation. This should give you TEA salt of your acid.
Good Luck
Another option, if hydrogenolysis conditions are compatible with your route, could be using a benzyl ester instead of a tert-butyl ester as protecting group. This way, you would be able to deprotect your carboxylic acid with H2 and Pd/C, and thus avoid the possibility of formation of TFA salts, as the isolation of your target compound upon completion of the hydrogenolysis should only require filtration on a Celite pad followed by the evaporation of your solvent.
I hope this helps,
Best regards
If the structure of the target compound permits, the method suggested by Thibault should certainly be the method of choice.
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