538
M. D. Mosher, L. G. Emmerich, K. S. Frost and B. Anderson
Vol 43
Methyl 3-(p-methoxyphenyl)-5-isoxazolinylacetate (2c).
1H nmr (deuterochloroform): ꢀ 7.73 (m, 4H), 7.4 (m, 8H), 6.70
(m, 2H), 5.05 (dddd, J= 10.2, 7.8, 7.2, 6.0Hz, 1H), 3.73 (s, 3H),
3.46 (dd, J=16.8, 10.2Hz, 1H), 3.04 (dd, J=16.8, 7.2Hz, 1H),
2.85 (dd, J=15.9, 6.0Hz, 1H), 2.62 (dd, J=15.9, 7.8Hz, 1H), 1.13
(s, 9H). 13C nmr (deuterochloroform): ꢀ 170.6, 157.4, 156.1,
135.4, 132.4, 130.1, 128.0, 127.9, 122.3, 120.0, 76.7, 51.9, 40.4,
39.6, 26.5, 19.5.
Flash chromatography (hexane:ethyl acetate 9:1) gave 99%
yield of the desired product as an off-white solid that agreed
with the literature data [1] for this compound. 1H nmr
(deuterochloroform): ꢀ 7.65 (m, 2H), 6.93 (m, 2H), 5.10 (dddd,
J=10.2, 7.8, 7.2, 6.0, 1H), 3.86 (s, 3H), 3.74 (s, 3H), 3.54 (dd,
J=16.8, 10.2Hz, 1H), 3.11 (dd, J=16.8, 7.2Hz, 1H), 2.89 (dd,
J=16.0, 6.0Hz, 1H), 2.66 (dd, J=16.0, 7.8Hz, 1H). 13C nmr
(deuterochloroform): ꢀ 170.8, 156.8, 144.5, 139.8, 129.5, 126.7,
77.1, 60.4, 52.5, 40.4, 39.1.
Anal. Calcd. for C28H31NO4Si: C, 71.00; H, 6.60; N, 2.96.
Found: C, 71.12; H, 6.48; N, 2.70.
Methyl 2-(3'-phenyl-5'-isoxazolinyl)acrylate (3).
Anal. Calcd. for C13H15NO4: C, 62.64; H, 6.07; N, 5.62.
Found: C, 62.90; H, 6.41; N, 5.73.
Flash chromatography (hexane:ethyl acetate 9:1) gave 62%
1
yield of the desired product as a slightly yellow solid. H nmr
Methyl 3-(p-fluorophenyl)-5-isoxazolinylacetate (2e).
(deuterochloroform): ꢀ 7.69 (m, 2H), 7.42 (m, 3H), 6.37 (m,
1H), 6.09 (m, 1H), 5.54 (dddd, J=11.0, 7.2, 0.9, 0.6Hz, 1H), 3.83
(s, 3H), 3.74 (dd, J=17, 11Hz, 1H), 3.20 (dd, J=17, 7.2Hz). 13C
nmr (deuterochloroform): ꢀ 165.8, 156.3, 138.8, 130.3, 129.3,
128.7, 126.7, 125.7, 78.6, 52.1, 41.9.
Flash chromatography (hexane:ethyl acetate 9:1) gave 60%
yield of the desired product as an off-white solid. mp 67-69°C.
1H nmr (deuterochloroform): ꢀ 7.53 (m, 2H), 6.95 (m, 2H), 4.98
(dddd, J=10.5, 7.5, 7.2, 6.3Hz, 1H), 3.59 (s, 3H), 3.40 (dd,
J=16.8, 10.5Hz, 1H), 2.99 (dd, J=16.8, 7.5Hz, 1H), 2.74 (dd,
J=15.9, 6.3Hz, 1H), 2.55 (dd, J=15.9, 7.2Hz, 1H). 13C nmr
(deuterochloroform): ꢀ 170.5, 163.5 (d, J13C-19F=250Hz), 155.5,
128.6 (d, J13C-19F=8Hz), 125.7 (d, J13C-19F=4Hz), 115.7 (d, J13C-
19F=22Hz), 77.1, 51.7, 40.1, 39.4. hrms (FAB) Calcd. for
C12H13NO3F: 238.08795; Found: 238.08746.
Anal. Calcd. for C13H13NO3: C, 67.52; H, 5.66; N, 6.05.
Found: C, 67.68; H, 5.91; N, 6.17.
REFERENCES AND NOTES
[1]J. B. Lubetsky, A. Dios, J. Han, B. Aljabari, B. Ruzsicska, R.
Mitchell, E. Lolis and Y. Al-Abed, J. Biological Chem., 277(28), 24976
(2002).
Anal. Calcd. for C12H12FNO3: C, 60.76; H, 5.10; N, 5.90.
Found: C, 61.08; H, 4.69; N, 5.51.
[2] Y. Al-Abed, I. Cvetkovic, D. Miljkovic, F. Nicoletti and S.
Stosic-Grujicic, Abstract MEDI 184 – 227th ACS National Meeting,
Anaheim, CA, 2004.
Methyl 3-(m-fluorophenyl)-5-isoxazolinylacetate (2f).
Flash chromatography (hexane:ethyl acetate 9:1) gave 15%
yield of the desired product as an off-white waxy solid. mp 44-
[3a] C. B. Xue, J. Wityak, T. M. Sielecki, D. J. Pinto, D. G. Batt,
G. A. Cain, M. Sworin, A. L. Rockwell, J. J. Roderick, S. Wang, M. J.
Orwat, W. E. Frietze, L. L. Bostrom, J. Liu, C. A. Higley, F. W. Rankin,
A. E. Tobin, G. Emmett, G. K. Lalka, J. Y. Sze, S. V. DiMeo, S. A.
Mousa, M. J. Thoolen, A. L. Racanelli, E. A. Hausner, T. M. Reilly, W.
F. DeGrado, R. R. Wexler and R. E. Olson, J. Med. Chem., 40, 2064
(1997); and [3b] J. Wityak, T. M. Sielecki, D. J. Pinto, G. Emmett, J. Y.
Sze, J. Liu, A. E. Tobin, S. Wang, B. Jiang, P. Ma, S. A. Mousa, R. R.
Wexler and R. E. Olson, J. Med. Chem., 40, 50 (1997).
[4] H. Zhang, W. H. Chan, A. W. M. Lee, P. F. Xia, W. Y.
Wong, Lett. Org. Chem., 1, 66 (2004).
[5] H. Alper, F. W. Hartstock and B. Despeyroux, Chem.
Commun., 905 (1984).
1
46°C. H nmr (deuterochloroform): ꢀ 7.30 (m, 3H), 7.01 (m,
1H), 5.04 (dddd, J=10.2, 7.5, 7.4, 6.0Hz, 1H), 3.64 (s, 3H), 3.44
(dd, J=16.5, 10.2Hz, 1H), 3.02 (dd, J=16.5, 7.5Hz, 1H), 2.79
(dd, J=15.9, 6.0Hz, 1H), 2.58 (dd, J=15.9, 7.4Hz, 1H). 13C nmr
(deuterochloroform): ꢀ 170.1, 169.5, 161.8 (d, J13C-19F=247Hz),
154.7 (d, J13C-19F=3Hz), 129.3 (d, J13C-19F=8Hz), 121.5 (d, J13C-
19F=3Hz), 116.1 (d, J13C-19F=21Hz), 112.5 (d, J13C-19F=23Hz), 77.3,
50.8, 39.0, 38.5. hrms (FAB) Calcd. for C12H13NO3F:
238.08795; Found: 238.08905.
Anal. Calcd. for C12H12FNO3: C, 60.76; H, 5.10; N, 5.90.
Found: C, 61.04; H, 5.10; N, 5.90.
[6] G. Zeni and R. C. Larock, Chem. Rev., 104, 2285 (2004); J.-
L. Malleron, J.-C. Fiaud and J.-Y. Legros, Handbook of Palladium-
Catalyzed Organic Reactions, Academic Press, New York, NY, 2000; J.
Tsuji, Palladium Reagents and Catalysts, John Wiley and Sons, New
York, NY, 1995.
Methyl 3-(2',5'-dimethoxyphenyl)-5-isoxazolinylacetate (2g).
Flash chromatography (hexane:ethyl acetate 9:1) gave 10%
yield of the desired product as an off-white solid. 1H nmr
(deuterochloroform): ꢀ 7.30 (m, 1H), 6.92 (m, 2H), 5.09 (dddd,
J=10.2, 7.5, 7.2, 6.5Hz, 1H), 3.82 (s, 3H), 3.80 (s, 3H), 3.74 (s,
3H), 3.66 (dd, J=17.4, 10.2Hz, 1H), 3.22 (dd, J=17.4, 7.2Hz,
1H), 2.86 (dd, J=15.9, 6.3Hz, 1H), 2.64 (dd, J=15.9, 7.5Hz, 1H).
13C nmr (deuterochloroform): ꢀ 170.8, 156.1, 153.5, 151.9,
119.0, 117.7, 113.3, 112.9, 77.1, 56.1, 55.8, 51.8, 42.7, 39.6.
hrms (FAB). Calcd. for C14H18NO5: 280.11850; Found:
280.11920.
[7] For leading references, see: [a] R. C. Larock and E. K. Yum, J.
Am. Chem. Soc., 113, 6689 (1991); [b] R. C. Larock, E. K. Yum, M. J.
Doty, and K. K. C. Sham, J. Org. Chem., 60, 3270 (1995); [c] T. Pei, and
R. A. Widenhoefer, J. Am. Chem. Soc. 123, 11290 (2001); [d] T. Pei, and
R. A. Widenhoefer, Chem. Commun., 650 (2002); [e] R. D. Walkup, and
M. D. Mosher, Tetrahedron 41, 9285 (1993); [f] R. D. Walkup, and M. D.
Mosher, Tetrahedron Lett., 35, 8545 (1994); [g] E. J. Stoner, B. A. Roden,
and S. Chembrukar, Tetrahedron Lett., 38, 4981 (1997); [h] Y. Tamaru, M.
Hojo, and Z. Yoshida, J. Org. Chem., 56, 1099 (1991); [i] S. Cacchi, G.
Fabrizi, and L. Moro, Tetrahedron Lett., 39, 5101 (1998) and references
therein; [j] R. D. Walkup, L. Guan, M. D. Mosher, S. W. Kim, and Y. S.
Kim, Synlett, 88 (1993); [k] W. F. J. Karstens, F. P. J. T. Rutjes, and H.
Hiemstra, Tetrahedron Lett., 38, 6275 (1997).
Anal. Calcd. for C14H17NO5: C, 60.21; H, 6.14; N, 5.01. Found
C, 60.42; H, 6.38; N, 5.27.
Methyl 3-(p-t-butyldiphenylsilyloxyphenyl)-5-isoxazolinyl-
acetate (2h).
[8a] R. D. Walkup and G. Park, Tetrahedron Lett., 29, 5505
(1988); [b] R. D. Walkup and G. Park, J. Am. Chem. Soc., 112, 1597
(1990); [c] T. Gallagher, I. W. Davies, S. W. Jones, D. Lathbury, M. F.
Mahon, K. C. Molloy, R. W. Shaw and P. Vernon, J. Chem. Soc., Perkin
Flash chromatography (hexane:ethyl acetate 9:1) gave 83%
yield of the desired product as an off-white solid. mp 52-60°C.