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22nd July 2012 @ 22:07
START: 23/07/12
FINISH: 23/07/12

Summary and Conclusion
Substrate scale: 104 mg (to 0.02 M).
Yb(OTf)3 loading: 5 mol%.
Solvent: THF.
Isolated yield: 27% (following chromatography).

Scheme%20KAB26-14.png
Table%20KAB26-14.png

Hazard and Risk Assessment
Hazard and Risk Assessment KAB26-4


Previous Experiments
Preparation of MNR42-1
Yb(OTf)3 catalysed acyl-PS to give 1-(6,7-dimethoxy-1-(4-nitrophenyl)-3,4-dihydroisoquinolin-2(1H)-yl)ethanone (KAB26-11)
Yb(OTf)3 catalysed (5 mol%) acyl-PS to give 1-(6,7-dimethoxy-1-(4-nitrophenyl)-3,4-dihydroisoquinolin-2(1H)-yl)ethanone (KAB26-12)

Chemical Information
2-(3,4-dimethoxyphenyl)-N-(4-nitrobenzylidene)ethanamine - 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 (KAB26-14) - 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
All THF was dried over 3 Å molecular sieves (1.5-2.5 mm) for >72 h
To a mixture of 3 Å molecular sieves in THF (17 mL) was dissolved MNR42-1 (104 mg, 0.331 mmol, 1 equiv.). The mixture was cooled in an acetone ice bath (-10 °C) before the addition of acetyl chloride (0.04 mL, 0.6 mmol, 1.7 equiv.) and 2,6-lutidine (0.06 mL, 0.5 mmol, 1.6 equiv.). Yb(OTf)3 (10 mg, 0.016 mmol, 0.05 equiv.) was added. The reaction mixture was allowed to warm to 25 °C and stirred under argon from 09:10.
After 1.5 hours, the reaction mixture was diluted with EtOAc (20 mL) and washed with saturated sodium bicarbonate solution (15 mL). The organic layer was separated. The aqueous layer was extracted with EtOAc (3 × 15 mL). The organic layers were combined, dried (MgSO4) and concentrated under reduced pressure before dry loaded onto a silica gel column.
Column chromatography (60-65%, EtOAc/hexane, v/v) of the crude product yielded KAB26-14 as a yellow solid (32 mg, 27%).

Summary and Conclusion
Substrate scale: 104 mg (to 0.02 M).
Yb(OTf)3 loading: 5 mol%.
Solvent: THF.
Isolated yield: 27% (following chromatography).

References
[1] D. Bradley, G. Williams and M. Lawton, J. Org. Chem. 2010, 75, 8351. DOI: 10.1021/jo101589h Paper.

Abbreviations Used:
EtOAc = ethyl acetate
TLC = thin layer chromatography
RM = reaction mixture
MS = molecular sieves
Soln = solution


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NOTES
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Linked Posts
Attached Files
Scheme KAB26-14
Table KAB26-14