Racemic Resolution of Praziquantel and Praziquanamine

 

Conversion of enantiopure R-(-)-Praziquanamine (PZQamine), obtained from the Scale-up: Racemic resolution of praziquanamine with (-)-Dibenzoyl-L-tartaric acid (MW49-12), to R-(-)-PZQ in order to determine the ee by chiral HPLC

See also:
From R-(-)-Praziquanamine to R-(-)-Praziquantel (MW48-1): N-Cyclohexanoyl-protection of the enantiopure PZQamine
From S-(+)-Praziquanamine to S-(+)-Praziquantel (MW48-2): N-Cyclohexanoyl-protection of the enantiopure PZQamine
N-Cyclohexanoyl-protection of the enantiopure R-(-)-PZQamine in a multigram scale (MW48-4)
N-Cyclohexanoyl-protection of the enantiopure R-(-)-PZQamine to PZQ (MW48-5)



Hazard and Risk Assessment:


Start time: 4:30 PM 7/12/2010
End time: 8:40 PM 7/12/2010


To a cooled solution of S-(+)Praziquanamine (150 mg, 743 µmol; M.W. = 202.3 g/mol) in DCM (5 mL) at 0°C was added triethylamine (112 mg, 155 µL, 1.11 mmol, 1.5 eq.; M.W.=101 g/mol, density=0.726g/mL) and cyclohexanoyl chloride (120 mg, 109 µL, 817 µmol, 1.1 eq.; M.W.=147 g/mol, density=1.096g/mL). The solution was stirred for 4 h at room temperature.
Work-up:
- quenched with water and stirred for further 15 min
- extracted with DCM, washed the organic layer with 1 N HCl solution
- column chromatography (EA, hexane = 1:1)

Yield: 228 mg (730 µmol, 98%) of a sticky solid (remaining solvent)
[M.W.=312.4 g/mol]
[α]D20 = -127° (c=1, EtOH)
(lit. [1] [α]D20 = 126.9 (c = 1, EtOH 99.%) [α]D20 = 135.0 (c = 1, CHCl3))
-> chiral HPLC

References:
[1] "Enantioselective synthesis of (R)-(−)-praziquantel (PZQ)", P. Roszkowski J. K. Maurin and Zbigniew Czarnocki, Tetrahedron: Asymmetry,2006, 17, 9, 15, 1415-1419. (doi:10.1016/j.tetasy.2006.04.023)

See: Optical rotation of R-(-)-PZQ and S-(+)-PZQ