Print version Print setup

Intramolecular nitrile oxide cyclization (INOC). Part II; N-cyclohexyl-2-(6-oxo-3a,4,6,7-tetrahydroisoxazolo[4,3-c]pyridin-5(3H)-yl)-2-phenylacetamide

SyntheticPage 487
DOI: 10.1039/SP487
Submitted Feb 14, 2011, published Feb 14, 2011
Sirin Gülten (siringulten@hotmail.com)
A contribution from Gülten Group, Çanakkale


			Reaction Scheme: Intramolecular nitrile oxide cyclization (INOC). Part II

Chemicals Used

N-allyl-N-(2-(cyclohexylamino)-2-oxo-1-phenylethyl)-3-nitropropanamide Gulten, S, SyntheticPages, 2011, 485
POCl3 (Acros Organics)
Et3N (Merck)
CHCl3
CH2Cl2
MgSO4

Procedure

A solution of  POCl3 (1.00 mmol, 0.093 mL) in CHCl3 (3.5 mL) was added dropwise to a mixture of N-allyl-N-(2-(cyclohexylamino)-2-oxo-1-phenylethyl)-3-nitropropanamide (0.670 mmol, 250 mg) and Et3N (2.68 mmol, 0.373 mL) in CHCl3 (3.5 mL). After 30 min Et3N (1.33 mmol, 0.186 mL) POCl3 (0.499 mmol, 0.0465 mL) in CHCl3 (1.5 mL) were added and the reaction mixture was stirred for 2 h at room temperature under nitrogen atmosphere at which point water (20 mL) was added. The crude product was extracted with CH2Cl2 (3 x 15 mL) and dried over anhydrous MgSO4. After evaporation of the organic solvent, the crude product was purified by flash chromatography using silica gel (eluent: ethyl acetate-hexane; 1 : 1) to obtain title compound as a white solid (168 mg, 71% yield,  mp 192-194 °C, Rf= 0.20   (ethyl acetate-hexane; 1 : 1). 50:50 Mixture of diastereoisomers as determined by 1H-NMR integration.

Author's Comments

The author thanks Çanakkale Onsekiz Mart University (BAP 2010/109) for financial support.

Data

IR-ATR:   3255, 3086, 2936, 2922, 2853, 1660, 1640, 1557 cm-1
1H NMR (400 MHz, DMSO-d6): ppm = 8.27 (1H, d, NH, J= 7.77 Hz), 7.43-7.33 (3H, m, aromatic CH), 7.23-7.20 (2H, m, aromatic CH), 6.29 (0.5H, s, CH-Ar), 6.22 (0.5H, s, CH-Ar), 4.34-4.27 (1H, m), 3.87-3.83 (1H, skew dd, CH2O), 3.81-3.77 (1H, skew t, CH2O), 3.71 (1H, m), 3.65-3.59 (2H, m), 3.57-3.51 (2H, m), 1.80-1.67 (4H, m, cyclohexyl CH2), 1.57-1.54 (1H, m, cyclohexyl CH2), 1.30-1.09 (5H, m, cyclohexyl CH2).
13C NMR (100 MHz, DMSO-d6): ppm = 167.86, 167.81, 166.38, 166.17, 155.47, 155.41, 135.92, 135.70, 128.74, 128.63, 128.60, 128.41, 127.95, 127.86, 70.31, 70.10, 59.76, 58.43, 47.72, 47.17, 46.31, 46.02, 45.84, 32.24, 32.12, 32.08, 32.06, 30.99, 25.11, 24.53, 24.44.

 


Lead Reference

1. Akritopoulou-Zanze, I.; Gracias, V.; Moore, J. D.; Djuric, S. W. Tetrahedron Lett., 2004, 45, 3421.
2. Gulten, S, SyntheticPages, 2011, 485

Other References

1. Loubinoux, B.; Gerardin, P.; Schneider, R.; Ahrach, M.; Boëlle, J. Trends Heterocycl. Chem. 1995, 4, 135.
2. Chiacchio, U.; Corsaro A.; Librando, V.; Rescifina, A.; Romeo, R.; Romeo, G. Tetrahedron, 1996, 52, 14323

Supplementary Information

inoc2 proton NMR.jpg
inoc2 carbon NMR.jpg

This page has been viewed approximately 3485 times since records began.

Get structure file (.cdx, .sk2, .mol)

Keywords: addition, amides, aromatics/arenes, heterocyclic compounds, intramolecular nitrile oxide cyclization (INOC), nucleophilic

Post new comment
Loading ...