合成路线1

The intermediate cyclopentanecarboxylic ester (XII) has been obtained as follows: The reaction of 2-oxaspiro[4.4]nonane-1,3-dione (XXVI) with the chiral auxiliary 4(S)-isopropyloxazolidin-2-one (XXVII) by means of BuLi in THF gives the addition product (XXVIII), which is protected as the benzyl ester (XXIX) with benzylbromide and DBU. The regioselective azidation of (XXIX) with 2,4,6-triisopropylbenzenesulfonyl azide and potassium bis(trimethylsilyl)amide affords the (S)-azide (XXX), which is treated with H2O2 in THF/water to eliminate chiral auxiliary and providing 2(S)-azido-2-[1-(benzyloxycarbonyl)cyclopentyl]acetic acid (XXXI). Condensation of (XXXI) with 1(R)-ethyl-2,2-dimethylpropylamine (XXXII) by means of HBTU in dichloromethane gives the corresponding amide (XXXIII), which is finally reduced at the azido group with SnCl2 in methanol to afford the target intermediate (XII). The intermediate 1(R)-ethyl-2,2-dimethylpropylamine (XXXII) has been obtained as follows: The reaction of 2,2-dimethyl-3-pentanone (XXXIV) with the chiral auxiliary 1(R)-phenylethylamine (XXXV) by means of TiCl4 in benzene gives N-(1(R)-ethyl-2,2-dimethylpropyl)-N-(1(R)-phenylethyl)amine (XXXVI), which is then hydrogenated with H2 over Pd/C in methanol to eliminate the chiral auxiliary and obtain the target amine (XXXII).