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

Synthetic Approach to Gain Insight into Antigenic Determinants of Cephalosporins: In Vitro Studies of Chemical Structure−IgE Molecular Recognition Relationships

“…To obtain the new third nuclear structure fragment, necessary to have model structures with a higher oxidation state at C-3 in the model structure, compounds 4 (FG = (OCH 3 ) 2 ), the amine nuclear structure fragment 15 was quantitatively obtained following an analogous methodology used for the synthesis of similar products, described in Scheme B. The methoxy acrylate 11 was converted to bromo acetal 12 with N -bromosuccinimide (NBS)/MeOH by a bromo etherification reaction of the alkene .…”

“…To obtain the new third nuclear structure fragment, necessary to have model structures with a higher oxidation state at C-3 in the model structure, compounds 4 (FG = (OCH 3 ) 2 ), the amine nuclear structure fragment 15 was quantitatively obtained following an analogous methodology used for the synthesis of similar products, described in Scheme B. The methoxy acrylate 11 was converted to bromo acetal 12 with N -bromosuccinimide (NBS)/MeOH by a bromo etherification reaction of the alkene . Reaction of 12 with an excess of n -butylamine at room temperature selectively afforded bromo amide 13 , and the nucleophilic displacement of bromide 13 took place with an excess of benzyl amine at higher temperatures to give product 14 .…”

“…The methoxy acrylate 11 was converted to bromo acetal 12 with N-bromosuccinimide (NBS)/MeOH by a bromo etherification reaction of the alkene. 30 Reaction of 12 with an excess of n-butylamine at room temperature selectively afforded bromo amide 13, and the nucleophilic displacement of bromide 13 took place with an excess of benzyl amine at higher temperatures to give product 14. The last step of hydrogenolysis with a Pearlman catalyst afforded the free primary amine 15.…”

“…This was synthesized as previously described. 30 Compound 13. An excess of n-butylamine (5.75 mL, 58.1 mmol) was added dropwise to stirred bromo acetal 12 (6 g, 26.4 mmol) under argon at 5 °C.…”

An Efficient, Practical Approach to the Synthesis of 2,4-Disubstituted Thiazoles and Oxazoles: Application to the Synthesis of GW475151

“…There have been many synthetic efforts surrounding the preparation of oxazoles 6 including rhodium(II)-catalysed reaction of diazocarbonyl compounds with nitriles, 7 oxidation of oxazolines, 8 Hantzsch-type condensation of amides and R-bromo ketones, 9 acid-catalyzed cyclisation of substituted iminoethers via the Cornforth protocol, 10 cyclodehydration of aldehydoamides using Ph 3 PI 2 11 and acid-mediated conversion of amide acetals. 12 Many of these routes have limitations in terms of yield, operation on kilogram scale, cost of reagents, and robustness. We sought an efficient route into the oxazole acid 3 that would be applicable to routine large-scale manufacture.…”