Racemic Resolution of Praziquantel and Praziquanamine

 

RXN 011 - Resolution of rac-PZQamine (MNR7-1) with (+)-dibenzoyl-D-tartaric acid (MNR5-1) to obtain S-PZQamine (MNR2-3)




Hazard and Risk Assessment:
As for MNR2-1

rac-PZQamine (13.92 g, 68.83 mmol) and (+)-dibenzoyl-D-tartaric acid. 2IPA (32.93 g, 68.83 mmol) was dissolved in a mixture of isopropanol (280 mL) and water (60 mL) by taking to reflux. The solution was allowed to cool to room temperature and stand overnight. The solid was then filtered and rinsed with IPA/water (5:1).

Crude salt (18.22 g, 32.61 mmol, 95%)



Mother liquor
Solvent was evaporated and solid residue was dried under high vac.
diastereomeric salt

The salt (18.22 g, 32.61 mmol) was dissolved in a mixture of i-PrOH (200 mL) and water (100 mL) by heating. It was then allowed to cool to room temperature and stand overnight (in an attempt to see if better crystallization could be achieved - it was)

The salt (13.78 g) was mixed with water (80 mL) and taken to pH 11 with the addition of NaOH solution (2M) and extracted with DCM (100 ml x 3). The aqueous layer was pH adjusted to pH2 using 2M HCl - see below. The organic fractions were combined, dried over magnesium sulphate, filtered and concentrated under reduced pressure to give an off white solid (3.38 g, 16.7 mmol, 49 %).

Again, why such a low yield?



MNR2-3 [α]D20 = +280° (c=1, DCM) (level 5 polorimiter was broken, used the old one on level 4)

1H NMR MNR2-3

Product used in
N-Cyclohexanoyl-protection of MNR2-3 to give S-PZQ (MNR1-3)

Lab book page complete, MNR