合成路线1

2) The reaction of 1-acetylcyclopropane-1-carboxylic acid (XIII) with 1(R)-phenylethylamine (IV) by means of ethyl chloroformate and triethylamine gives the corresponding amide (XIV), which is treated with ethylene glycol and p-toluenesulfonic acid, yielding the dioxolane (XV). The bromination of (XV) with Br2 in dioxane affords the bromomethyl-dioxolane (XVI), which is cyclized by means of NaH in DMF to give 5-[1(R)-phenylethyl]-5-azaspiro[2.4]heptane-4,7-dione 7-ethyleneketal (XVII). Opening of the ketal ring with 1N HCl in refluxing acetone yields the free diketone (XVIII), which by reaction with hydroxylamine and triethylamine in ethanol affords the monooxime (XIX). The reduction of (XIX) with H2 over RaNi in methanol gives the aminoketone (XX) as a diastereomeric mixture, which is separated by column chromatography yielding 7(S)-amino-5-[1(R)-phenylethyl]-5-azaspiro[2.4]heptan-4-one (XXI). The reduction of (XXI) with LiAlH4 in THF affords the amine (XXII), which is protected with 2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile in THF to give 7(S)-(tert-butoxycarbonylamino)-5-[1(R)-phenylethyl]-5-azaspiro[2.4]heptane (XXIII). Finally, this compound is hydrogenolyzed with H2 over Pd/C in ethanol, yielding the desired chiral spiro compound (II).