4-acyl-2.4-disubstituted-5 -oxazolones

FIGURE 7.34 Decomposition of the symmetrical anhydride of A-methoxycarbonyl-valine (R1 = CH3) in basic media.2 (A) The anhydride is in equilibrium with the acid anion and the 2-alkoxy-5(4//)-oxazolone. (B) The anhydride undergoes intramolecular acyl transfer to the urethane nitrogen, producing thelV.AT-fcwmethoxycarbonyldipeptide. (A) and (B) are initiated by proton abstraction. Double insertion of glycine can be explained by aminolysis of the AA -diprotected peptide that is activated by conversion to anhydride Moc-Gly-(Moc)Gly-0-Gly-Moc by reaction with the oxazolone. (C) The A,A -diacylated peptide eventually cyclizes to the IV.AT-disubstituted hydantoin as it ejects methoxy anion or (D) releases methoxycarbonyl from the peptide bond leading to formation of the -substituted dipeptide ester. 

TABLE 7.20. SYNTHESIS OF SATURATED 4-ACYL-2,4-DISUBSTITUTED 5(4H)-OXAZOLONES VIA ACYLATION OF 2,4-DISUBSTITUTED 5(4H)-OXAZOLONES AT C-4... 

Mohapatra and Datta isolated a series of 2,4-disubstituted-5-(f-butoxycarbon-yloxy)oxazoles 546 by treating A -acyl amino acids 544 with di-ferf-butyl pyroca-bonate (Boc)20 (Scheme 1.150). The authors proposed that (Boc>20 effected cyclodehydration of 544, producing a 2,4-disubstituted 5(4//)-oxazolone 545. However, enolization of 545 under the reaction conditions and trapping with (Boc)20 then led to 546. Attempts to isolate 545 were unsuccessful. This one-pot reaction was quite general and afforded the oxazoles in good yield. 

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