A chemoselective, acid mediated conversion of amide acetal to oxazole: The key step in the synthesis of cardiovascular drug, ifetroban sodium

Tetrahedron Letters

Volumn 39, Issue 27, 1998, Pages 4769-4772

  Swaminathan, Shankar ^a   Singh, Ambarish K ^a   Li, Wen Sen ^a   Venit, John J ^a   Natalie Jr , Kenneth J ^a   Simpson, James H ^a   Weaver, Raymond E ^a   Silverberg, Lee J ^b  

^a BRISTOL MYERS SQUIBB   (United States)

^b BRISTOL MYERS SQUIBB COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETAL DERIVATIVE; AMIDE; CARDIOVASCULAR AGENT; IFETROBAN; OXAZOLE;

ARTICLE; CHEMICAL ANALYSIS; CHEMICAL REACTION; DRUG STRUCTURE; DRUG SYNTHESIS;

EID: 0032474717     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)00904-6     Document Type: Article

References (16)

1. 1. (a) Carmeli, S.; Moore, R. E.; Patterson, G. M. L.; Corbett, T. H.; Valeriote, F. A. J. Am. Chem. Soc. 1990, 112, 8195.
2. (b) Jansen, R.; Kunze, B.; Reichenbach, H.; Jurkiewicz, E.; Hunsmann, G.; Höfle, G. Liebigs Ann. Chem, 1992, 357.
3. 2. Hassner, A.; Fischer, B. Heterocycles 1993, 35, 1441. For natural products see Wipf, P.; Venkataraman, S. Synlett. 1997, 1.
4. 2. Hassner, A.; Fischer, B. Heterocycles 1993, 35, 1441. For natural products see Wipf, P.; Venkataraman, S. Synlett. 1997, 1.
5. 3. (a) Barrish, J. C.; Singh, J.; Spergel, S. H.; Han, W-C.; Kissick T. P.; Kronenthal, D. R., Mueller, R. H. J. Org. Chem. 1993, 58, 4494-4496.
6. (b) A. I. Meyers protocol using cuprous bromide and t-butyl perbenzoate fails in cases of 4-carboxy amide oxazolines, see Meyers A. I., Tavares F., Tetrahedron Lett. 1994, 35, 2481-2484.
7. (c) D. R. Williams, P. D. Lowder, Y-G. Gu, D. A. Brooks, Tetrahedron Lett. 1997, 38, 331-334.
8. (d) Evans, D. A.; Gage, J. R.; Leighton, J. L. J. Am. Chem. Soc. 1992, 114, 9434. see also Oxazoles; Turchi, I. J.; Ed.; Wiley; New York, 1986 for other methods.
9. (d) Evans, D. A.; Gage, J. R.; Leighton, J. L. J. Am. Chem. Soc. 1992, 114, 9434. see also Oxazoles; Turchi, I. J.; Ed.; Wiley; New York, 1986 for other methods.
10. 4. Wipf, P.; Miller, C. P. J. Org. Chem. 1993, 58, 3604-3606.
11. 5. Robinson, R. J. Chem. Soc. 1909, 95, 2167.
12. 6. There is precedence for Lewis acid mediated cylization of amide glycosides to oxazolines (Kusama, T.; Soga, T.; Shioya, E.; Nakayama, K.; Nakajima, H.; Osada, Y.; Ono, Y.; Kusumoto, S.; Shiba, T.; Chem Pharm Bull 1990, 38, 3366). In another instance a glycosidic oxazoline has been transformed to an oxazole (Gigg, R., Warren, C. D., J. Chem. Soc. (C) 1968, 1903).
13. 6. There is precedence for Lewis acid mediated cylization of amide glycosides to oxazolines (Kusama, T.; Soga, T.; Shioya, E.; Nakayama, K.; Nakajima, H.; Osada, Y.; Ono, Y.; Kusumoto, S.; Shiba, T.; Chem Pharm Bull 1990, 38, 3366). In another instance a glycosidic oxazoline has been transformed to an oxazole (Gigg, R., Warren, C. D., J. Chem. Soc. (C) 1968, 1903).
14. 7. Three other routes to the amide acetal 5 were evaluated which will be published elsewhere.
15. 8. Misra, R. N.; Brown, B. R.; Sher P. M.; Patel, M. M.; Hall, S. E.; Han, W-C.; Barrish, J. C.; Kocy, O.; Harris, D. N.; Goldenberg, H. J.; Michel, I. M.; Schumacher, W. A.; Webb, M.; Monshizadegan, H.; Ogletree, M. L. J. Med Chem. 1993, 36, 1401.
16. 2, p-toluenesulfonic acid, trifluoroacetic acid and methanesulfonic acid. A combination of titanium tetrachloride and collidine in methylene chloride gave inferior quality oxazole with modest yields. Philip Sher in our Drug Discovery group used the titanium tetrachloride and collidine combination on substrates analogous to the amide acetal 7 and reported low yields with significant impurity profile.