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18th July 2012 @ 04:21
START: 18/07/12
FINISH: 19/07/12


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)

Chemical Information
2-(3,4-dimethoxyphenyl)-N-(4-nitrobenzylidene)ethanamine (KAB23-2) - 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 (KAB26-11) - 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.

MNR42-1 (205 mg, 0.652 mmol, 1 equiv.) was dissolved in anhydrous acetonitrile (30 mL). The clear yellow solution was cooled in a brine ice bath before the addition of acetyl chloride (0.05 mL, 0.652 mmol, 1 equiv.) and 2,6-lutidine (0.05 mL, 0.652 mmol, 1 equiv.). Yb(OTf)3 (0.021 g, 0.034 mmol, 0.05 equiv.) was added. The reaction mixture was allowed to warm to ambient temperature and stirred under argon from 14:20.
At 15:20, an aliquot (1.5 mL) was extracted and diluted with EtOAc (10 mL). The mixture was washed with saturated sodium bicarbonate solution (10 mL). The organic fraction was separated and the aqueous layer further extracted with EtOAc (3 × 10 mL). The organic fractions were combined, dried over magnesium sulfate, filtered then concentrated under reduced pressure to give a yellowish semi-solid (10 mg).
At 17:30 the remainder of the reaction mixture was diluted with EtOAc (30 mL) and the mixture was triturated off the MS. The solution was washed with saturated sodium bicarbonate solution (30 mL). The organic layer was separated. The aqueous layer was extracted with EtOAc (3 × 30 mL). The organic fractions were combined, dried (MgSO4) and concentrated under reduced pressure to give crude KAB26-12 (390 mg, 168%).
Crude KAB26-12

The crude product was purified by silica gel column chromatography (60% EtOAc/Hexane, v/v) yielding the KAB26-12 as a yellow solid (205 mg, 88%).

Summary and Conclusion
Yb(OTf)3 catalyst loading: 5 mol%.
Reaction time: 3 hours.
Temperature: Ambient.
Substrate Scale: 200 mg.
Isolated Yield: 88% (following chromatography).

[1] S. W. Youn, The Journal of Organic Chemistry 2006, 71, 2521-2523. DOI: 10.1021/jo0524775. Paper
[2] K. Manabe, D. Nobutou, S. Kobayashi, Bioorg. Med. Chem. 2005, 13, 5154-5158.

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

Linked Posts
Attached Files
Scheme KAB26-12
Table KAB26-12
Crude KAB26-12