US 2004/0171849 A1 · Process for producing optically active azetidine-2-carboxylic acid

Abstract

The present invention provides an efficient, simple, and commercially advantageous process for producing optically active azetidine-2-carboxylic acid, which is an important material for medicines. The process includes the steps of halogenating an optically active N-protected 4-amino-2-hydroxybutyric acid following inversion of the configuration to produce an optically active N-protected 4-amino-2-halobutyryl halide; hydrolyzing the halide; deprotecting the amino group of the hydrolyzed product to produce an optically active 4-amino-2-halobutyric acid; cyclizing the product in an alkaline aqueous solution; and then protecting the amino group of the cyclized product to produce an optically active N-protected azetidine-2-carboxylic acid. The present invention also provides an optically active N-protected 4-amino-2-halobutyryl halide represented by general formula (2): 1 (wherein P represents a protective group for the primary amino group; * indicates that the carbon atom is asymmetric; and each of X and Y independently represents a halogen atom), which is useful for producing the optically active azetidine-2-carboxylic acid.

Claims18

Dependent claims

A process for producing an optically active N-protected 4-amino-2-halobutyryl halide represented by general formula (2):

7
(wherein P represents a protective group for the primary amino group;
* indicates that the carbon atom is asymmetric;
and each of X and Y independently represents a halogen atom), the process comprising halogenating an optically active N-protected 4-amino-2-hydroxybutyric acid following inversion of the configuration, the optically active N-protected 4-amino-2-hydroxybutyric acid being represented by general formula (1):
8
(wherein p and * are as defined above):

3 more elements

A process for producing an optically active azetidine-2-carboxylic acid represented by general formula (4):

14
(wherein * indicates that the carbon atom is asymmetric), the process comprising the steps of:
halogenating an optically active N-protected 4-amino-2-hydroxybutyric acid following inversion of the configuration, the optically active N-protected 4-amino-2-hydroxybutyric acid being represented by general formula (1):
15
(wherein P represents a protective group for the primary amino group;
and * is as defined above) to produce an optically active N-protected 4-amino-2-halobutyryl halide represented by general formula (2):
16
(wherein P and * are as defined above;
and each of X and Y independently represents a halogen atom);
hydrolyzing the optically active N-protected 4-amino-2-halobutyryl halide represented by general formula (2) to produce an optically active N-protected 4-amino-2-halobutyric acid represented by general formula (3):
17
(wherein P, *, and X are as defined above);
deprotecting the amino group of the optically active N-protected 4-amino-2-halobutyric acid represented by general formula (3);
and
cyclizing the deprotected product in an alkaline aqueous solution.

12 more elements

A process for producing an optically active N-protected azetidine-2-carboxylic acid represented by general formula (5):

18
(wherein A represents a protective group for the secondary amino group;
and * indicates that the carbon atom is asymmetric), the process comprising the steps of:
halogenating an optically active N-protected 4-amino-2-hydroxybutyric acid following inversion of the configuration, the optically active N-protected 4-amino-2-hydroxybutyric acid being represented by general formula (1):
19
(wherein P represents a protecting group for the primary amino group;
and * is as defined above) to produce an optically active N-protected 4-amino-2-halobutyryl halide represented by general formula (2):
20
(wherein P and * are as defined above;
and each of X and Y independently represents a halogen atom);
hydrolyzing the optically active N-protected 4-amino-2-halobutyryl halide represented by general formula (2) to produce an optically active N-protected 4-amino-2-halobutyric acid represented by general formula (3):
21
(wherein P, *, and X are as defined above);
deprotecting the amino group of the optically active N-protected 4-amino-2-halobutyric acid represented by general formula (3);
cyclizing the deprotected product in an alkaline aqueous solution to produce an optically active azetidine-2-carboxylic acid represented by general formula (4):
22
(wherein * is as defined above);
and
reacting the optically active azetidine-2-carboxylic acid represented by general formula (4) with an amino group-protecting agent.

16 more elements

Dependencies are inferred from the claim text.

Process for producing optically active azetidine-2-carboxylic acid

Life of this patent

Process for producing optically active azetidine-2-carboxylic acid

Life of this patent

Abstract

Claims18