Pictet-Spengler route to Praziquantel

 

****Experiment concluded on 06/02/12. Conclusion pending.




Hazard and Risk Assessment


Previous Related Experiments
Preparation of 2-(3,4-Dimethoxyphenyl)ethyl isocyanide (MNR4-2)
Preparation of the PZQ analogue Ugi-intermediate (KAB5-1)
Preparation of the N-benzoyl PZQ analogue Ugi-intermediate (KAB6-1)

Following Experiments

Procedure

01/02/12
A mixture of paraformaldehyde (2.29 g, 76.2 mmol), cyclohexanecarboxylic acid (9.77 g, 76.2 mmol), 2,2-diethoxyethylamine (10.15 g, 76.2 mmol) in methanol (76 mL) was cooled in a brine ice bath. KAB4-2 (~10 g, 76 mmol) was added dropwise to the mixture at 0 °C, turning the white solution yellow. The reaction mixture was allowed to warm to room temperature and stirred from 14:00.


03/02/12
At 12:00 (+46 hours) The reaction mixture was concentrated under reduced pressure and the dark brown liquid residue was dissolved in ether (150 mL) then washed with water (100 mL) and brine (100 mL). The organic layer was dried over magnesium sulfate before the solvent was removed in vacuo to give crude KAB5-2 as a dark yellow-brown oil (31 g).

TLC of the crude product in EtOAc/hexane, 3:1, v/v showed two spots. One corresponding to the expected product and a polar baseline spot.
The crude product was dissolved in EtOAc (25 mL) then passed through a short silica gel column eluting with neat EtOAc. The yellow filtrate was concentrated under reduced pressure to give KAB5-2 as a dark yellow oil .


06/02/12
The KAB5-2 final product was dried under a high vacuum before analysis by H-NMR. Yield: 28.0 g, 91%.


References
[1] H. Cao, H. Liu, A. Doemling, Chemistry-a European Journal 2010, 16, 12296 (DOI: 10.1002/chem.201002046)

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NOTES 01/02/12
- Reaction mixture started turning a pale orange colour during the addition of KAB4-2.
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