PROCESS FOR PRODUCTION OF 2,5-DIOXOPYRROLIDINE-3-CARBOXYLATE

摘要

Disclosed is a novel intermediate which enables to produce a tetrahydropyrrolo[1,2-a]pyrazine-4-spiro-3'-pyrrolidine derivative, such as ranirestat which is expected as a therapeutic agent for a diabetic complication, in a short process step, at a low cost and in a safe manner. Also disclosed is a process for producing the intermediate. Specifically disclosed is a process for producing a compound represented by the formula (I) [wherein R¹ represents an amino group protected by a protecting group or the like; and R² represents a lower alkyl group or the like], which comprises the following steps (1) and (2): (1) converting a cyano group in a compound represented by the formula (II) [wherein n and m independently represent a number of 0 or 1, provided that m is 1 and R² and R³ independently represent a protecting group for a carboxy group when n is 0, and m is 0 and R² and R³ independently represent a protecting group for a carboxy group when n is 1; and R¹ is as defined above] into a carbamoyl group in the presence of a bivalent palladium compound, a primary amide and water; and (2) cyclizing the product of the step (1). (I)(II)