合成路线1

The intermediate amide (IV) can be obtained by two related methods. The homochiral methylenesuccinate (I) was coupled with piperidine (II) in the presence of EDC and HOBt to afford amide (III). Subsequent stereoselective conjugate addition of methylamine produced the (R,R)-amine (IV). In a related procedure, conjugate addition of methylamine to unsaturated ester (V) gave adduct (VI). Acid cleavage of the tert-butyl ester of (VI) generated carboxylic acid (VII), which was then coupled with piperidine (II) to provide (IV). Sulfonamide (VIII) was prepared by condensation of amine (IV) with methanesulfonyl chloride. Hydrogenolysis of the benzyl ester of (VIII) yielded acid (IX), which was finally coupled with hydroxylamine producing the title hydroxamic acid.