Racemic Resolution of Praziquantel and Praziquanamine

 

RXN 002 - Resolution of rac-PZQamine with (-)-di-p-anisoyl-L-tartaric acid (MW46-6) to obtain S-(+)-PZQamine (MNR2-1)

See:
Hydrolysis of rac-PZQ (MW2-14)
Repetition: Synthesis of (+)-Di-p-anisoyl-D-tartaric acid (MW46-6)




Hazard and Risk Assessment:


reaction on 0930
reaction off 1300

rac-PZQamine (1.0 g, 4.94 mmol) and (-)-di-p-anisoyl-L-tartaric acid (2.07 g, 4.94 mmol) was dissolved in a mixture of isopropanol (20 mL) and water (2 mL) by heating. The solution was allowed to cool to room temperature and stand for 3 hours. The solid was then filtered and rinsed with IPA/water (5:1, 50 mL).

Crude salt (2.597 g, 4.18 mmol, 85 %)

The salt (2.597 g, 4.18 mmol) was dissolved in NaOH solution (2M, 75 mL) and extracted with DCM (75 ml x 2). The aqueous layer was pH adjusted to pH2 using 6M HCl - see below. The organic fractions were combined, dried over magnesium sulphate, filtered and concentrated under reduced pressure to give a cloudy white thick oil (0.263 g, 1.30 mmol, 26 %). The oil was taken up in refluxing IPA/Water (5:1, 10 mL) and left to stand overnight at room temperature. No crystals formed over night (too dilute?) so mixture was concentrated under reduced pressure and extracted with DCM (15 mL) and brine (15 mL), dried over magnesium sulphate, filtered and concentrated to give the oil as before. Upon drying on the high vac the oil slowly crystallized. Optical rotation of this showed the undesired enantiomer

MNR2-1 [α]D20 = -268° (c=1, DCM)

reaction not taken any further and moved onto MNR2-2



1H NMR - resolved product


Lab book page complete, MNR