Pictet-Spengler route to Praziquantel

 

START: 03/05/12
FINISH:

TO DO:
NMR.

Background
Repeat of experiment KAB26-2 in order to obtain an accurate yield for the procedure.




Hazard and Risk Assessment
As for KAB26-2


Previous Experiments
Yb(OTf)₃ catalysed PS reaction to give 6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline (KAB21-9)
TFA catalysed synthesis of 6,7-dimethoxy-1-(4-nitrophenyl)-1,2,3,4-tetrahydroisoquinoline (KAB24-4)
Lewis acid-catalyst screen for the PS reaction to give KAB21 and KAB24
AuCl₃/AgOTf catalysed acyl-PS reaction to give 1-(6,7-dimethoxy-1-(4-nitrophenyl)-3,4-dihydroisoquinolin-2(1H)-yl)ethanone (KAB26-1 & KAB26-2)

Following Experiments

Chemical Information
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.
1-(6,7-dimethoxy-1-(4-nitrophenyl)-3,4-dihydroisoquinolin-2(1H)-yl)ethanone (KAB26-3) - SMILES: O=[N+]([O-])C1=CC=C(C2N(C(C)=O)CCC3=CC(OC)=C(OC)C=C32)C=C1, InChI: InChI=1S/C19H20N2O5/c1-12(22)20-9-8-14-10-17(25-2)18(26-3)11-16(14)19(20)13-4-6-15(7-5-13)21(23)24/h4-7,10-11,19H,8-9H2,1-3H3, InChIKey: OIFIJKJQAGAGKY-UHFFFAOYSA-N.

Procedure
03/05/12. Gold(III) chloride trihydrate (20.5 mg, 0.052 mmol, 1 mol%) and silver triflate (27.0 mg, 0.105 mmol, 2 mol%) were vigorously stirred in MeCN (5 mL) for 50 minutes. KAB23-1 (1.6 g, 5.205 mmol, 1 equiv.) was dissolved in MeCN (260 mL) before the sequential addition of acetyl chloride (0.4 mL, 5.2 mmol, 1 equiv.) and 2,6-lutidine (0.6 mL, 5.2 mmol, 1 equiv.) at rt. The KAB23-1 solution was added to the gold/silver mixture. The reaction mixture was left to stir at rt from 18:30.

All TLCs were eluted with 50% EtOAc/hexane, v/v and stained with KMnO₄.

After 15 hours, the reaction mixture was concentrated under reduced pressure, before purification by silica gel column chromatography, eluting with 50-100% EtOAc/hexane, v/v.

Combined fractions 4-14
R_f:
Mass: 352 mg

Combined fractions 39-49
R_f:
Mass: 8 mg

Combined fractions 51-55
Mass: 19 mg

Combined fractions 56-65
Mass: 465 mg

Combined fractions 66-81
R_f:
Mass: 477 mg

82-86

87+

Summary and Conclusion

References
[1] S. W. Youn, The Journal of Organic Chemistry 2006, 71, 2521-2523. DOI: 10.1021/jo0524775. Paper


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NOTES 04/05/12
Remaining fractions to be combined and concentrated first thign next week.
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