Patent ID: 8633001

Claim:
A process for producing an optically active succinimide derivative represented by the formula (I): [in the formula (I), R 3 represents a lower alkyl] or a salt thereof, which comprises the following steps (A) to (D), and further comprises the step (E), if necessary: (A) the step of reacting an aminomalonate derivative represented by the formula (II): [in the formula (II), R 1 represents amino or an amino protected with a protective group, and two of R 3 represent the same lower alkyls having the same meaning as defined above] and a halogenated acetic acid ester derivative represented by the formula (III): [Formula 3] Y—CH 2 CO 2 R 2 (III) [in the formula (III), R 2 represents a lower alkyl, and Y represents a halogen] in the presence of a base for conversion into an ester derivative represented by the formula (IV): [in the formula (IV), each of R 1 , R 2 , and R 3 has the same meaning as defined above] or a salt thereof, (B) the step of allowing an enzyme that is a pig liver esterase or a rabbit liver esterase to react on the ester derivative represented by the formula (IV) or a salt thereof for conversion into an optically active carboxylic acid derivative represented by the formula (V): [in the formula (V), each of R 1 , R 2 , and R 3 has the same meaning as defined above] or a salt thereof, (C) the step of reacting the optically active carboxylic acid derivative represented by the formula (V) or a salt thereof with an ammonia source in the presence of a condensing agent, or reacting the optically active carboxylic acid derivative represented by the formula (V) or a salt thereof with an activating reagent and then reacting the resultant with an ammonia source, for conversion into an optically active amide derivative represented by the formula (VI): [in the formula (VI), each of R 1 , R 2 , and R 3 has the same meaning as that defined above] or a salt thereof, (D) the step of allowing a base to react on the optically active amide derivative represented by the formula (VI) or a salt thereof for conversion into an optically active succinimide derivative represented by the formula (I) or (VII): [in the formula (VII), R 1A represents an amino protected with a protective group, and R 3 has the same meaning as defined above] or a salt thereof, and (E) the step of eliminating the protective group on R 1A of the optically active succinimide derivative represented by the formula (VII) or a salt thereof for conversion into an optically active succinimide derivative represented by the formula (I) or a salt thereof.