Patent ID: 7678760

Claim:
A method of preparing a Leu* Ala dipeptide isostere, comprising the steps of: a) reacting ethyl propiolate and N-(tert-butoxycarbonyl)-leucinal in the presence of n-butyl lithium or lithium diisopropyl amine to form ethyl-5-{(tert-butoxycarbonyl)amino}-4-hydroxy-7-methyloct-2-ynoate represented by the following structural formula: b) reacting the ethyl-5-{(tert-butoxycarbonyl)amino}-4-hydroxy-7-methyloct-2-ynoate with hydrogen in the presence of Pd/BaSO 4 to form an intermediate; c) reacting the intermediate with an acid to form 5-{1′-{(tert-butoxycarbonyl)amino}-3′-methylbutyl}-dihydrofuran-2(3H)-one represented by the following structural formula: d) reacting iodomethane with 5-{1′-{(tert-butoxycarbonyl)amino}-3-methylbutyl}-dihydrofuran-2(3H)-one in the presence of hexamethyldisilazane to form 5-{1′-{(tert-butoxycarbonyl)amino}-3′-methylbutyl}-3-methyl-dihydrofuran-2(3H)-one represented by the following structural formula: e) reacting 5-{1′-{(tert-butoxycarbonyl)amino}-3′-methylbutyl}-3-methyl-dihydrofuran-2(3H)-one with a base to form a Leu* Ala dipeptide isostere represented by the following structural formula: