Synthesis of (Z)-4-(acylamino)- and 4-(alkylamino)-α-oximinophenylacetic acids: properties and stereochemical determination

Article abstract of DOI:10.1021/jo00314a029

The preparation, properties, and stereochemical determinations of a series of 4-substituted α-oximinophenylacetic acids are described.The 4-acetamino and 4-<<(benzyloxy)carbonyl>amino>-α-oxophenylacetic acids 7 and 19 were synthesized from the corresponding acetophenones with selenium dioxide.The oximes were then prepared and their stereochemistry determined as Z (syn), through the chemical properties of the methoxyimino derivatives.A key intermediate was (Z)-methyl 4-<<(benzyloxy)carbonyl>amino>-α-<<(tetrahydro-2H-pyran-2-yl)oxy>imino>phenylacetate (24), which was synthesized from the free oxime or from the keto acid by using O-(tetrahydropyran-2-yl)hydroxylamine.Deprotection of this compound at nitrogen gave the 4-amino-α-oximino ester, 25, which was acylated with a variety of acid chlorides and hydrolyzed to the 4-(acylamino)-α-oximinophenylacetic acids.By employment of methyl 4-amino-α-oxophenylacetate dimethyl ketal (9), a general reductive amination process was developed, leading to the 4-(alkylamino)-α-oximinophenylacetic acids.