4-Methyl-2-oxovaleric acid → 4,4-Dimethoxy-2-isobutylbutanoic acid

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Reaction Steps

Alternatively, for those compounds wherein n=1 and R1 is H, the compounds can be prepared by condensing the ylide 1,1-dimethoxy-2-(triphenylphosphoranylidene) ethane prepared from triphenylphosphine and 1,1-dimethoxy-2-bromoethane with 4-methyl-2-oxopentanoic acid. The product is then hydrogenated to obtain 4,4-dimethoxy-2-isobutylbutanoic acid which is coupled to the moiety R3NHCHR4COX to obtain 4,4-dimethoxy-2-isobutylbutanoyl--NR3CHR4COX. Treatment with aqueous acid yields the aldehyde 2-isobutyl-4-oxobutanoyl--NR3CHR4COX. The oxime is prepared by reaction with hydroxylamine and reduced to the corresponding N-substituted hydroxylamine. Acylation of both the hydroxaminol oxygen and nitrogen followed by hydrolysis of the O-acyl group provides the N-acyl reverse hydroxymates. (Summers, J.B., et al., J Med Chem (1988) 31:1960-1964.)

Provenance & Evidence