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28th May 2011 @ 09:15
Previously synthesized enantioenriched praziquanamine (PZQamine) was converted to the desired enantioenriched/enantiopure R-(–)-Praziquantel through reacting with cyclohexanoyl chloride.

PZQ Synthesis BMSPDYL 3-2


To resolved PZQamine (0.1558 g) was added triethylamine (0.12 mL, 1.5 eq.) and methylene dichloride (4 mL). Cyclohexanoyl chloride (0.12 mL, 1.1 eq.) was added dropwise to the mixture at 0°C and the mixture was stirred at room temperature for 21 hours.

Work-up:
The reaction was then quenched with 1.1 mL of deionized water and stirred for a further 30 minutes. The reaction mixture was separated and the organic layer washed, in this order, with 2 mL of 10% sodium carbonate, 2 mL of 0.5N HCl, and 2 mL brine. After drying with NaSO4, the solvent was evaporated off using a rotary evaporator and the product stored at 5°C for 24 hours.

Yield: 0.1161 g; 48%
Appearance: clear, orange-ish oil

IR (Thin Film): 3053.99 cm-1 (sp2 C–H stretch), 2935.92 cm-1 (sp2 C–H stretch), 2856.92 cm-1 (sp3 C–H stretch), 1648.89 cm-1 (C=O stretch), ~1600 cm-1 (C=C aromatic stretch), 1421.91 cm-1 (C=C aromatic stretch), 1266.43 cm-1 (C–N stretch)

1H NMR (400 MHz, CDCl3): (δ 7.26 ppm, m), (δ 5.3 ppm, s), (δ 0.0 ppm, s, TMS)
(NMR sample was too dilute)

HPLC: R-(-)PZQ 94=6.6% -> 93.2%ee
Astec Chirobiotic T Column, Methanol/(79.9:0.1 Water/H3PO4 = 50/50, 1.0 ml/min flow rate, 2018 psi, RT: (R-(-)PZQ): 3.80 min, (S-(+)PZQ): 4.95 min, (R-(-)PZQamine): 7.53 min, (S-(+)PZQamine): 8.03 min

References:
(1) Woelfe, M. et al. "The Resolution of Praziquantel". 2011. http://openwetware.org/wiki/Todd:PZQ_Resolution
Attached Files
28th May 2011 @ 09:02
Previously synthesized enantioenriched praziquanamine (PZQamine) was converted to the desired enantioenriched/enantiopure R-(–)-Praziquantel through reacting with cyclohexanoyl chloride.

PZQ Synthesis BMSPDYL 3-1


To resolved PZQamine (0.1645 g) was added triethylamine (0.12 mL, 1.5 eq.) and methylene dichloride (4 mL). Cyclohexanoyl chloride (0.12 mL, 1.1 eq.) was added dropwise to the mixture at 0°C and the mixture was stirred at room temperature for 21 hours.

Work-up:
The reaction was then quenched with 1.1 mL of deionized water and stirred for a further 30 minutes. The reaction mixture was separated and the organic layer washed, in this order, with 2 mL of 10% sodium carbonate, 2 mL of 0.5N HCl, and 2 mL brine. After drying with NaSO4, the solvent was evaporated off using a rotary evaporator and the product stored at 5°C for 24 hours.

Yield: 0.1190 g; 47%
Appearance: clear, colorless oil

IR (Thin Film): 3053.86 cm-1 (sp2 C–H stretch), 2935.12 cm-1 (sp2 C–H stretch), 2856.53 cm-1 (sp3 C–H stretch), 1648.69 cm-1 (C=O stretch), ~1600 cm-1 (C=C aromatic stretch), 1421.95 cm-1 (C=C aromatic stretch), 1263.35 cm-1 (C–N stretch)

1H NMR (400 MHz, CDCl3): (δ 7.26 ppm, m), (δ 5.3 ppm, s), (δ 0.0 ppm, s, TMS)
(NMR sample was too dilute)

HPLC: R-(-)PZQ 94.6% -> 89.2%ee
Astec Chirobiotic T Column, Methanol/(79.9:0.1 Water/H3PO4 = 50/50, 1.0 ml/min flow rate, 2018 psi, RT: (R-(-)PZQ): 3.78 min, (S-(+)PZQ): 4.92 min, (R-(-)PZQamine): 7.47 min, (S-(+)PZQamine): 7.88 min

References:
(1) Woelfe, M. et al. "The Resolution of Praziquantel". 2011. http://openwetware.org/wiki/Todd:PZQ_Resolution
Attached Files
28th March 2011 @ 02:15
Previously synthesized enantioenriched praziquanamine (PZQamine) was converted to the desired enantioenriched/enantiopure R-(–)-Praziquantel through reacting with cyclohexanoyl chloride.

PZQ Synthesis BM 3-1


To resolved PZQamine (0.30 g) was added triethylamine (0.2302 g, 1.5 eq.) and methylene dichloride (8 mL). Cyclohexanoyl chloride (0.2402 g, 1.1 eq.) was added dropwise to the mixture at 0°C and the mixture was stirred at room temperature for 45 hours.

Work-up:
The reaction was then quenched with 1 mL of deionized water and stirred for a further 30 minutes. The reaction mixture was separated and the organic layer washed, in this order, with 5 mL of 10% sodium carbonate, 5 mL of 0.5N HCl, and 5 mL brine. After drying with NaSO4, the solvent was evaporated off using a rotary evaporator and the product stored at 5°C for 24 hours.

Yield: 0.3846 g; 83%
TLC (Silica; 1:1 Hexanes : EtOAc; CAM Visualization): 2 spots; Rf1 = 0.34, Rf2 = 0.91
Appearance: white solid/powder
Melting Point: 113°C – 123°C

IR (Thin Film): 3490.75 cm-1 (N–H stretch), 3052.22 cm-1 (sp2 C–H stretch), 2928.21 cm-1 (sp2 C–H stretch), 2855.01 cm-1 (sp3 C–H stretch), 1722.49 cm-1 (C=O stretch), 1647.45 cm-1 (C=O amide stretch), ~1600 cm-1 (C=C aromatic stretch), 1450.07 cm-1 (C=C aromatic stretch), 1297.62 cm-1 (C–N stretch)

1H NMR (300 MHz, CDCl3): (δ 7.3 ppm, m), (δ 5.3 ppm, s, DCM), (δ 5.2 ppm, m), (δ 5.0 ppm, m), (δ 4.8 ppm, m), (δ 4.5 ppm, m), (δ 4.1 ppm, d), (δ 3.9 ppm, d), (δ 2.9 ppm, m), (δ 2.5 ppm, m), (δ 2.2 ppm, s), (δ 1.9 ppm, m), (δ 1.3 ppm, m), (δ 0.0 ppm, s, TMS)

1H NMR (300 MHz, CDCl3, Eu(hfc)3): (δ 7.3 ppm, m), (δ 5.3 ppm, s, DCM), (δ 5.1 ppm, m), (δ 4.6 ppm, s), (δ 3.0 ppm, m), (δ 2.3 ppm, m), (δ 2.2 ppm, s), (δ 1.8 ppm, m), (δ 1.3 ppm, m), (δ 0.4 ppm, d), (δ 0.0 ppm, s, TMS)

Polarimetry: [α]589nm = –127° (c = 1.039, DCM)

Enantiomeric Excess: 90%

References:
(1) Woelfe, M. et al. "The Resolution of Praziquantel". 2011. http://openwetware.org/wiki/Todd:PZQ_Resolution
Attached Files