Ethyl-(R,S)-5-acetyl-4,5-dihydro-3-isoxazole Acetate

Pier Giovanni Baraldi; Barbara Cacciari; Romeo Romagnoli; Giampiero Spalluto

doi:10.3390/M47

,

and

Department of Pharmaceutical Sciences, University of Ferrara, Via Fossato di Mortara 17-19, I-44100 Ferrara, Italy

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Author to whom correspondence should be addressed.

Molecules1998, 3(2), M47;https://doi.org/10.3390/M47

This article belongs to the Section Molbank Section of Molecules, 1997-2001

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The isoxazoline 3 was prepared by the [3+2] cycloaddition of the nitroderivative 1 [1] with methyl vinyl ketone 2 under Mukaiyama conditions [2].

Phenyl isocyanate (2.5 ml, 23 mmol) was slowly added (4 h) to a mixture of ethyl-nitropropionate 1 (1.46 g, 10 mmol) and methyl vinyl ketone 2 (1.6 ml, 20 mmol) in dry benzene (60 ml) containing a few drops of Et3N. The mixture was stirred at room temperature for two days. The suspension was filtered to eliminate the precipitate of diphenylurea and to the filtrate was added H2O (100 ml). The resulting biphasic system was stirred for two hours at room temperature. After separation, the organic phase was dried and concentrated in vacuo. The crude residue was purified by flash chromatography (ether/light petroleum = 7:3) to give the desired compound 3 as a yellow oil (1 g, 50%).

TLC (ether/light petroleum = 6:4) Rf 0.42

IR (neat, cm^-1): 2985, 1737, 1722, 1599, 1555, 1503, 1444, 1400, 1381, 1260, 1203, 1096, 1027.

¹HNMR (CDCl3) d: 4.9 (dd, 1H, J = 9.4 Hz, 4.2 Hz, CH2CHO); 4.18 (q, 2H, J = 7.2 Hz, CO2CH2CH3);

3.07 (dd, 1H, J = 17.2 Hz, J = 9.4 Hz, CHHCHO); 2.76 (dd, 1H, J = 17.2 Hz, 4.2 Hz, CHHCHO); 2.54 (d, 2H, J = 7 Hz, CH2CO2); 2.17 (s, 3H, COCH3); 1.25 (t, 3H, J = 7.2 Hz, CO2CH2CH3)

Anal. calc. for C9H13NO4 (199.20): C 54.26, H 6.58, N 7.03; found: C 54.61, H 6.65, N 7.10

Acknowledgment

We gratefully acknowledge the Ministero Pubblica Istruzione (Grant 40% and 60%) for their generous support.

References

Taylor, M. D.; Badger, E. W.; Steffen, R. P.; Haleen, S. J.; Pugsley, T. A.; Shih, Y. H.; Weishaar, R. E. 2-(2-Aryl-2-oxoethylidene)-1,2,3,4-tetrahydropyridines. Novel isomers of 1,4-dihyropyridine calcium channel blockers. J. Med. Chem. 1988, 31, 1659. [Google Scholar] [CrossRef]
Mukaiyama, T.; Hoshino, T. The reactions of primary nitro paraffins with isocyanates. J. Am. Chem. Soc. 1960, 82, 5339. [Google Scholar] [CrossRef]
Baraldi, P. G.; Bigoni, A.; Cacciari, B.; Caldari, C.; Manfredini, S.; Spalluto, G. Nitrile oxide [3+2] cycloaddition: application to the synthesis of 6-substituted 3(2H)- pyridazinones and 6- substituted 4,5-Dihydro-4-hydroxy-3 (2H)-pyridazinones. Synthesis 1994, 11, 1158. [Google Scholar] [CrossRef]

Sample availability: Available from the authors.

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