Racemic Resolution of Praziquantel and Praziquanamine

 

Mnr: 1-10
Preparation of starting material for the scaled-up racemic resolution of PZQamine



Hazard and Risk Assessment:


Procedure:
rac-PZQ (13.0 g, 41.6 mmol) was dissolved in a mixture of EtOH (80 mL) and 1M HCl (420 mL) and heated to reflux for 14 h. The solution was allowed to cool to room temperature then cooled in an ice bath, basified with NaOH pellet (approx 22 g, pellets used to minimise volume of aqueous material) to pH 12-13 and extracted with DCM (4 x 150 mL). The organic fractions were combined, dried over magnesium sulphate, filtered and concentrated under reduced pressure to give a clear oil which was placed on the high vac for 4 hours by which time the oil had crystallized into white crystals

Reaction repeated a total of 4 times to bring through enough material.

Batch 1+2 combined:- 18.96 g, 113%

Recrystallized in toluene:hexane (9:1) and left in the freezer overnight. Crystals filtered off in the morning and washed with hexane.

Off white/pale orange crystals:- 14.28 g, 85%

Batch 3+4 (as above)

White crystals:- 13.92 g, 83%

Characterisation



1H NMR (CDCl3, 300 MHz): d = 7.29-7.10 (m, 4H), 4.94-4.75 (m, 2H), 3.80-3.47 (m, 3H), 3.07-2.60 (m, 4H), 1.85 (s, 1H).



13C NMR (CDCl3, 75 MHz): d= 167.4, 135.1, 134.4, 129.5, 127.2, 126.8, 124.8, 57.0, 50.2, 50.0, 38.9, 29.0.

m.p. 117–118 °C

lit m.p. 116-118 Laurent, S. A. L., J. Boissier, et al. (2008). "Synthesis of “Trioxaquantel”® Derivatives as Potential New Antischistosomal Drugs." European Journal of Organic Chemistry 2008(5): 895-913.


Product used in

Resolution of rac-PZQamine with (-)-dibenzoyl-L-tartaric acid to obtain R-(-)-PZQamine (MNR3-2)
Resolution of rac-PZQamine with (+)-dibenzoyl-D-tartaric acid to obtain S-PZQamine (MNR2-3)

Lab book page complete, MNR