Method for producing amino acid derivatives
The present invention aims to provide a method for producing a (2S,5R)-5-(protected oxyamino)-piperidine-2-carboxylic acid derivative at a low cost that can be performed under mild reaction conditions not requiring a facility at an extremely low temperature, is safer, can control the quality of the desired product with ease, and shows good workability in the site of production. A method for producing a compound represented by the formula (2): wherein PG 1 is an amino-protecting group, PG 2 is an amino-protecting group, PG 3 is a hydroxyl-protecting group, LG is a leaving group, and R is a hydrocarbon group having 1-8 carbon atoms and optionally having substituent(s), including a step of reacting a compound represented by the formula (1): wherein each symbol is as defined above, with a hydroxylamine derivative represented by the formula PG 2 NHOPG 3 wherein each symbol is as defined above, in the presence of a base in a solvent.
1. A compound represented by any one of the following formula (2a), (2b), (3b) or (5a):
wherein Boc is a tert-butoxycarbonyl group, Ac is an acetyl group, Ns is a p-nitrobenzenesulfonyl group, and Bn is a benzyl group.
2. A method for producing a compound represented by the formula (4):
wherein R is a hydrocarbon group having 1-8 carbon atoms and optionally having one or more substituents, and PG 3 is a hydroxyl-protecting group,
or a salt thereof, comprising
reacting a compound represented by the formula (1):
wherein PG 1 is an amino-protecting group, LG is a sulfonyloxy group, and R is as defined above,
with a hydroxylamine derivative represented by the formula PG 2 NHOPG 3 , wherein PG 2 is an amino-protecting group and PG 3 is as defined above, in the presence of a base in a solvent to obtain a compound represented by the formula (2):
wherein each symbol is as defined above;
removing PG 2 from the aforementioned compound represented by the formula (2) to obtain a compound represented by the formula (3):
wherein each symbol is as defined above,
or a salt thereof; and
removing PG 1 from the aforementioned compound represented by the formula (3).
3. A method for producing a compound represented by the formula (4):
wherein R is a hydrocarbon group having 1-8 carbon atoms and optionally
having one or more substituents, and PG 3 is a hydroxyl-protecting group, or a salt thereof, comprising
reacting a compound represented by the formula (1):
wherein PG 1 is an amino-protecting group, LG is a sulfonyloxy group, and R is as defined above,
with a hydroxylamine derivative represented by the formula PG 2 NHOPG 3 , wherein PG 2 is an amino-protecting group and PG 3 is as defined above, in the presence of a base in a solvent to obtain a compound represented by the formula (2):
wherein each symbol is as defined above;
removing PG 1 from the aforementioned compound represented by the formula (2) to obtain a compound represented by the formula (5):
wherein each symbol is as defined above,
or a salt thereof; and
removing PG 2 from the aforementioned compound represented by the formula (5) to obtain the compound represented by the formula (4).