Cleavage experiment with PZQ using 50 vol% TFA

15 Feb
Published by Michael Wolfle

This experiment was conducted in order to examine whether the cyclohexanoyl amid bond could be cleaved under mild acidic conditions by using a 50 vol% TFA solution in DCM. After 48 h under refluxing temperature 99% of the starting material could be recovered.
As a result, this procedure can be used for the scission of acid-labile protecting groups of prospective derivatives of PZQ without touching the cyclohexanoyl group.
rac-PZQ 1 (500 mg, 1.60 mmol) was dissolved in a mixture of DCM (3 mL) and TFA (3 mL) and heated to reflux for 48 h. The solution was made basic to pH 12 by adding 5 N NaOH solution and extracted with DCM. The combined organic layers were washed with basic brine and dried over sodium sulfate. After removing of the solvent under reduced pressure, only the starting material rac-PZQ 1 (493 mg, 1.58 mmol, 99%) could be isolated.