Method for producing cis-5-hydroxy-2-piperidinecarboxylic acid derivative, and method for purifying cis-5-hydroxy-2-piperidinecarboxylic acid
The present invention aims to provide a method for purifying cis-5-hydroxy-2-piperidinecarboxylic acid with high purity, and a method for producing its derivative. The present invention provides a method for producing a cis-5-hydroxy-2-piperidinecarboxylic acid derivative, which method comprises a step of converting cis-5-hydroxy-2-piperidinecarboxylic acid into a compound(s) of Formula (1) and/or Formula (2) (wherein R 1 represents a protective group for an amino group, and R2 represents a C 1 -C 6 alkyl group), and a method for purifying cis-5-hydroxy-2-piperidinecarboxylic acid.
1. A method for producing a compound of Formula (1), said method comprising a step of reacting a mixture containing cis-5-hydroxy-2-piperidinecarboxylic acid and an impurity with a single kind of an acid halide, an acid anhydride, an acid halide and an acid anhydride in a single reactor to convert said cis-5-hydroxy-2-piperidinecarboxylic acid into a compound of Formula (1) by protecting and lactonizing said cis-5-hydroxy-2-piperidinecarboxylic acid with the single kind of the acid halide, the acid anhydride, or the acid halide and the acid anhydride in the single reactor,
wherein R 1 represents a protective group for an amino group, and
wherein the impurity comprises trans-5-hydroxy-2-piperidinecarboxylic acid.
2. The method according to claim 1 , further comprising the step of synthesizing cis-5-hydroxy-2-piperidinecarboxylic acid by bacterial reaction and/or enzymatic reaction.
3. The method according to claim 1 , further comprising a step of separating the compound of Formula (1) by crystallization or solvent extraction.
4. The method according to claim 1 , wherein said impurity further comprises (2S,3S)-3-hydroxy-2-piperidinecarboxylic acid.
5. The method according to claim 1 , wherein a mixture containing cis-5-hydroxy-2-piperidinecarboxylic acid and an impurity is reacted with a single kind of an acid halide.
6. The method according to claim 5 , wherein said acid halide comprises benzyloxycarbonyl chloride.
7. The method according to claim 1 , wherein:
the single kind of the acid halide, the acid anhydride, or the acid halide and the acid anhydride comprises the R 1 protective group;
the single kind of the acid halide, the acid anhydride, or the acid halide and the acid anhydride protects the amino group with the R 1 protective group in the compound of Formula (1); and
the single kind of the acid halide, the acid anhydride, or the acid halide and the acid anhydride allows the lactonization of the cis-5-hydroxy-2-piperidinecarboxylic acid to convert the cis-5-hydroxy-2-piperidinecarboxylic acid into the compound of Formula (1).
8. The method according to claim 1 , further comprising a step of separating the compound of Formula (1) by solvent extraction.