Pictet-Spengler route to Praziquantel

 

START: 26/04/12
FINISH:

Altering conditions slightly from KAB25-1.



Hazard and Risk Assessment


Previous Experiments
Yb(OTf)₃ catalysed PS to give 6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline (KAB25-1)
Lewis acid-catalyst screen for the PS reaction to give KAB21 and KAB24

Following Experiments

Chemical Information


Procedure
(All glassware was ovendried prior to use.)
26/04/12. Yb(OTf)₃ (120 mg, 0.194 mmol) was added to a 3-necked flask containing well dried 3Å powdered MS under a nitrogen atmosphere. Dry toluene (30 mL) was added via canula before the sequential addition of benzaldehyde (0.10 mL, 0.97 mmol) and 3,4-dimethoxyphenethylamine (0.16 mL, 0.97 mmol). The reaction mixture was reflux heated to 110 °C from 10:00.


Monitoring the Reaction Progress by TLC
All TLCs were eluted with 15%, MeOH/DCM, v/v and stained with ninhydrin. Lane 19-2 corresponds to the isolatable imine intermediate and 25-2 corresponds to the reaction mixture. Co = cospot.


Mini-workup (5 mL extraction)
Mass: 40.6 mg

After 4 days, the reaction mixture was allowed to cool. The reaction mixture was quenched with saturated sodium bicarbonate solution, and the organic fraction was removed. The basic aqueous layer was extracted with EtOAc (3 × 30 mL). The organic fractions were combined, dried over magnesium sulfate, filtered, then concentrated under reduced pressure to give crude KAB25-2 (359 mg, 133%).

Summary and Conclusion


References
[1] K. Manabe, D. Nobutou, S. Kobayashi, Bioorg. Med. Chem. 2005, 13, 5154-5158.
[2] M. J. V. Eynden, K. Kunchithapatham, J. P. Stambuli, Journal of Organic Chemistry 2010, 75, 8542-8549.


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NOTES 27/04/12
- Still no product after >30 hours. Will leave over weekend.

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