Pictet-Spengler route to Praziquantel

 

START: 17/04/12
FINISH: 19/04/12




Hazard and Risk Assessment


Previous Experiments
TFA catalysed synthesis of 6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline (KAB21-4)
TFA mediated synthesis of 6,7-dimethoxy-1-(4-nitrophenyl)-1,2,3,4-tetrahydroisoquinoline (KAB24-3)
TFA catalysed synthesis of 6,7-dimethoxy-1-(4-nitrophenyl)-1,2,3,4-tetrahydroisoquinoline (KAB24-4)

Following Experiments
Yb(OTf)₃ catalysed PS to give 6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline (KAB25-1)
Yb(OTf)₃ catalysed PS to give 6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline (KAB25-2)

Chemical Information
N-[2-(3,4-Dimethoxyphenyl)ethyl]-1-phenylmethanimine (KAB19-2) SMILES: O(c1ccc(cc1OC)CC/N=C/c2ccccc2)C, InChI: InChI=1S/C17H19NO2/c1-19-16-9-8-14(12-17(16)20-2)10-11-18-13-15-6-4-3-5-7-15/h3-9,12-13H,10-11H2,1-2H3/b18-13+, InChIKey: HEYKSOUNCDDROU-QGOAFFKASA-N
2-(3,4-dimethoxyphenyl)-N-(4-nitrobenzylidene)ethanamine (KAB23-1) - SMILES: O=[N+]([O-])C1=CC=C(/C=N/CCC2=CC(OC)=C(OC)C=C2)C=C1, InChI: InChI=1S/C17H18N2O4/c1-22-16-8-5-13(11-17(16)23-2)9-10-18-12-14-3-6-15(7-4-14)19(20)21/h3-8,11-12H,9-10H2,1-2H3/b18-12-, InChIKey: LMBMXYXQVBPKHJ-PDGQHHTCSA-N.
6,7-Dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline (KAB21-X) - SMILES: O(c1c(OC)cc3c(c1)C(c2ccccc2)NCC3)C, InChI: InChI=1S/C17H19NO2/c1-19-15-10-13-8-9-18-17(12-6-4-3-5-7-12)14(13)11-16(15)20-2/h3-7,10-11,17-18H,8-9H2,1-2H3, InChIKey: GZGZWZVAJDFXJK-UHFFFAOYSA-N
6,7-dimethoxy-1-(4-nitrophenyl)-1,2,3,4-tetrahydroisoquinoline (KAB24-X) - SMILES: O=[N+]([O-])C1=CC=C(C2NCCC3=CC(OC)=C(OC)C=C32)C=C1, InChi: InChI=1S/C17H18N2O4/c1-22-15-9-12-7-8-18-17(14(12)10-16(15)23-2)11-3-5-13(6-4-11)19(20)21/h3-6,9-10,17-18H,7-8H2,1-2H3, InChIKey: GITFNMZGMQLGOX-UHFFFAOYSA-N.

Pre-Procedure



Procedure


On at 13:45.

After 24 hours, the reactions were quenched with saturated sodium bicarbonate (6 equiv. volumes), then extracted with EtOAc. The organic fractions were combined, dried over magnesium sulfate, filtered, then concentrated under reduced pressure to give the crude products.




Summary and Conclusion
H-NMR of all crude products indicated

References
[1] K. Manabe, D. Nobutou, S. Kobayashi, Bioorg. Med. Chem. 2005, 13, 5154-5158.


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NOTES 16/04/12
- Put 2 × 25 mL volumetric flasks, the vials+stirrers and the Schlenk flask in the oven (1h).
- Activate 3A MS. Put under the high vac.
- Put KAB19-2, KAB23-1 and the Cu(OTf)₂ under the high vac.
- Prepare 10 balloons.
- Make up stock solutions. Plug in numbers into spreadsheet. Upload spreadsheet.
- Weigh out catalysts. Put in vials. Add MS. (Carefully!) Evacuate vials. Put under argon (w/ balloons).
- Add stock solutions. Start time zero.

WORKUP:
- Quench with 6 × volume saturated sodium bicarbonate. Extract with EtOAc.
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