Urea derivatives, alkyl acyl preparation

Matthews et al. described a synthetic route to hydantoins as well as thio-hydantoins on solid-supported esters in 1997 [136,137]. The hydantoin or thiohydantoin skeleton is synthesized on Wang resin by addition of an amino acid and following reductive alkylation. For the release of hydantoins, acylation with an isocyanate to urea derivatives with following base promoted cleavage takes place. For the preparation of thiohydantoins, isothiocyanates have to be reacted with the corresponding precursors these intermediates cyclize without additional treatment with bases to the corresponding thiohydantoins. 

Trifluoromethylmalonic acid derivatives were used in the synthesis of 5-trifluoromethyl-substituted pyrimidines. In particular, acyl fluorides 827 were obtained by alkylation of trifluoromethyhnalonyl fluoride (826), in turn prepared from acyl fluoride 825 (Scheme 164) [509], Reaction of 827 with urea led to the formation of fluorinated barbitmates 828. 

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