Pictet-Spengler route to Praziquantel

 

START: 12/04/12
FINISH: 13/04/12



Hazard and Risk Assessment
As for KAB21-2 (here).

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

Following Experiments

Chemical Information
N-[2-(3,4-Dimethoxyphenyl)ethyl]-1-phenylmethanimine (1, 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
6,7-Dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline (2, KAB21-3) - 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


Procedure
12/04/12. KAB19-2 (377 mg, 1.40 mmol, 1 equiv.) was dissovled in toluene (40 mL) before the addition of trifluoroacetic acid (0.20 mL, 2.80 mmol, 2 equiv.) at rt. The reaction mixture was reflux heated to 110 °C from 12:45.
13/04/12. After 25 hours, the reaction mixture was allowed to cool, then diluted with ethyl acetate (30 mL). The mixture was quenched with saturated sodium bicarbonate solution (80 mL) and the organic fraction was isolated. The aqueous fraction was further extracted with ethyl acetate (2 × 50 mL). The organic fractions were combined, dried over magnesium sulfate, filtered, then concentrated under reduced pressure to give crude KAB21-3 as a brown oil (248 mg, 66%).

Monitoring the Reaction Progress by TLC
All TLCs were eluted with 15%, methanol/dichloromethane, v/v and stained with ninhydrin.


Summary and Conclusion
NMR suggested most of the crude product were the hydrolysis products (based on large aldehyde peak). (MORE TO WRITE)
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NOTES
- Yellow spot in TLC corresponds to cyclised product.
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