4-oxazoleacetic acid esters

Moriya and co-workers prepared a series of potential hypolipidemic p-aminopyrroles from 4-oxazoleacetic acid esters. Thus polyphosphate ester (PPE) cyclodehydration of an aspartic acid diamide p-ester 851 produced a 2-aryl-5-(dialkylamino)-4-oxazoleacetic acid ethyl ester 852 (Scheme 1.229). Treatment of... 

The intermediate A -[(3.Sj-tctrahydro-5-oxo-3-furanyl]-benzenecarboxarnide (3) and the tert-butylthio ester of 4,5-dihydro-2-phenyl-4-oxazoleacetic acid have both also been used successfully in diastcrcosclectivc alkylations5. In these cases the diastereoselectivities are opposite to that observed for the amides and thus complement the amide reaction5. 

Meguro and co-workers used this method, among others, to prepare a variety of potential antidiabetic agents. For example, cyclization of cyclohexanecarbox-amide with ethyl 4-chloroacetoacetate gave 2-cyclohexyl-4-oxazoleacetic acid 199, albeit in poor yield (Scheme 1.54). Similarly, Ohkubo and co-workersprepared 4-(nitrophenyl)-2-phenyl-5-oxazolecarboxylic acid ethyl esters 200a and 200b as precursors to potential cerebral protective agents. 

Malamas and co-workers ° adapted Meguro and Fujita s methodology to prepare a series of 2-aryl-5-methyl-4-oxazoleacetic acid methyl esters 203, which... 

Thionyl chloride is one of the most common and effective reagents to effect cyclodehydration of 2-acylamino ketones. For example, Litak and Kauffman refluxed 446 in SOCI2 and isolated 4-[2-(3,4-dihydro-2//-l-benzopyran-6-yl)oxazol-5-ylpyridine 447 in excellent yield (Scheme 1.123). Both 447 and 441 were starting materials for reactive fluorescent stains to be used in fluorescence microscopy. Reck and Friedrichsen refluxed 448 in SOCl2/chloroform and prepared 4-(methoxy-carbonyl)-2-methyl-5-oxazoleacetic acid methyl ester 449 (Scheme 1.123). This material was a precursor of the novel diene 4-methoxy-2-methyl-furo[3,4-ti]ox-azole-6-carboxylic acid methyl ester 450. 

That these reactions proceed via the intermediacy of a Diels-Alder cycloaddition adduct has been affirmed by the isolation of a variety of the 1 1 Diels-Alder adducts.For example, the reaction of 5-ethoxy-4-methyloxazole 8 with cis-2,5-dimethoxy-2,5-dihydrofuran 9 provided the isolable endo and exo adducts 10 and 11 respectively, in a 2 1 ratio (Fig. 3.4). Similarly, 5-ethoxy-4-oxazoleacetic acid ethyl ester 12 reacted with maleic anhydride to provide the stable endo and exo adducts 13 and 14, in which the olefin has moved into conjugation with the ester moiety. In this case, compound 13 was the sole product when the reaction proceeded at 10°C, but only the exro-adduct 14 was isolated if the cycloaddition was conducted at 80°C. Heating at 50°C for 3h converted 13 into 14. The 2-carboethoxy analog of oxazole 12 behaved similarly. ... 

PYRROLECARBOXYLIC ACID ETHYL ESTERS FROM 2-ARYL-5-(DIALKYLAMINO)-4-OXAZOLEACETIC ACID ETHYL ESTERS UNDER VILSMEIER-HAACK CONDITIONS, 186... 

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