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 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), wherein the leaving group is a sulfonyloxy group,
comprising
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.
2. The production method according to claim 1 , wherein PG 1 is a carbamate type protecting group or an amide type protecting group, and a σ p − value thereof is not more than 1.00.
3. The production method according to claim 1 ,
wherein the compound represented by the formula (1) and the hydroxylamine derivative represented by the formula:PG 2 NHOPG 3 wherein PG 2 is an amino-protecting group, PG 3 is a hydroxyl-protecting group, and other symbols are each as defined above, are reacted at 10° C. -70° C.