合成路线1

A new procedure suitable for the large-scale preparation of (IV) was further described. The chiral bromide (VI) was obtained by diazotization of L-aspartic acid beta-methyl ester (V) in the presence of KBr. Subsequent displacement of the bromide ion of (VI) by the potassium salt of benzyl mercaptan with inversion of the configuration yielded sulfide (VII). The carboxyl group of (VII) was then reduced to alcohol (VIII) using borane-dimethyl sulfide complex, and subsequent treatment with SOCl2 and pyridine afforded chloride (IX). Cyclization of (IX) with ammonia in MeOH generated pyrrolidinone (X), which was converted to the pyrrolidinethione (XI) by treatment with P2S5. Cleavage of the benzyl protecting group of (XI) with sodium in liquid ammonia then gave the required thiol (IV).