Method for purifying pyruvic acid compounds

Details Method for purifying pyruvic acid compounds Method for purifying pyruvic acid compounds

1999-06-21

2002-02-19

Wilson, James O. (Department: 1623)

Organic compounds -- part of the class 532-570 series

Organic compounds

Carboxylic acid esters

C560S168000

Reexamination Certificate

active

06348617

ABSTRACT:

This application is the national phase under 35 U.S.C. §371 of PCT International Application No. PCT/JP97/03595 which has an International filing date of Oct. 8, 1997 which designated the United States of America.
1. Technical Field
The present invention relates to a method for purifying pyruvic acid compounds.
2. Background Art
Pyruvic acid compounds are useful as intermediates for the synthesis of drugs or amino acids, and as disclosed in JP-A 55-81845, for example, they have been used as intermediates for the production of antihypertensives. Ethyl 7-halo-2-oxoheptanoate, which is also a pyruvic acid compound, is an important intermediate of cilastatin. For the production thereof, there has been known a process in which an organic magnesium compound is reacted with diethyl oxalate according to the following scheme 1 (see JP-A 58-77885).
There has been known another process, for example, according to the following scheme 2, in which the synthesis is achieved by the reaction of a halide with ethyl 1,3-dithian-2-carboxylate and the subsequent deprotection [see J. Med. Chem., 30, 1074(1987)].
However, as described in the above references, the process according to scheme 1 has a defect in that the use of diethyl oxalate in excess makes the resulting pyruvic acid compound contaminated with diethyl oxalate and the process according to scheme 2 has a defect in that the use of a halide in excess and a base such as sodium hydride in mineral oil makes the resulting pyruvic acid compound contaminated with the halide and the mineral oil. Therefore, for obtaining pyruvic acid compounds, it requires the purification of intermediates or final pyruvic acid compounds by rectification or column chromatography.
For this reason, there has been sought a simple and easy method for purification by which the respective intermediates for synthesis or pyruvic acid compounds with high purity can be obtained without subjecting to a technique such as distillation or column chromatography.
Under these circumstances, the present inventors have intensively studied to develop a method in which pyruvic acid compounds can be purified by simple and easy procedures without using distillation, chromatography or any other techniques. As a result, they have found that the purification of a pyruvic acid compound can be achieved with high purity in a simple and easy manner by reacting the pyruvic acid compound with a bisulfite to give a bisulfite adduct of the pyruvic acid compound and then decomposing the adduct with an acid, thereby completing the present invention.
DISCLOSURE OF THE INVENTION
The present invention thus provides a method for purifying a pyruvic acid compound of general formula (I):
wherein R
1
is an optionally substituted lower alkyl group, an optionally substituted lower alkenyl group, an optionally substituted lower alkynyl group, an optionally substituted cycloalkyl group, an optionally substituted aryl group, or an optionally substituted heterocyclic group, and R
2
is an optionally substituted lower alkyl, which method is characterized in that the pyruvic acid compound of general formula (I) is reacted with a bisulfite of general formula (II):
MHSO
3
  (II)
wherein M is NH
4
or an alkali metal, to give a bisulfite adduct of the pyruvic acid compound and the adduct is then decomposed with an acid.
The present invention further provides a process for producing a pyruvic acid compound of general formula (VIII):
wherein R
3
is an optionally substituted lower alkyl group or an optionally substituted aryl group, and R
4
is an optionally substituted lower alkyl group, with higher purity using the above purification method, as well as a bisulfite adduct of the pyruvic acid compound of general formula (VIII).
DETAILED DESCRIPTION OF THE INVENTION
It seems that the adduct of the pyruvic acid compound of general formula (I) with the bisulfite of formula (II) according to the present invention may have a structure such as a sulfonic acid (e.g., the structure disclosed in Bull. Chem. Soc. Jpn., 40, 2703(1967)), a sulfurous acid ester, or a molecular compound (e.g., the structure described in JP-A 3-34948), similarly to the case of an adduct of an aldehyde with a bisulfite (see, e.g., “Dai-Yuhkikagaku (4th ed.)”, vol. 3, pp. 56-57, published on Aug. 30, 1964, Asakura-shoten; J. Org. Chem., 6, 888(1941)). The adduct of the pyruvic acid compound of general formula (I) with the bisulfite of general formula (II) according to the present invention may include those having the structures in all these cases.
In the pyruvic acid compounds of general formula (I) according to the present invention, the optionally substituted lower alkyl group in the substituent R
1
may include, for example, straight-chain or branched C
1
-C
8
alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, neopentyl, n-hexyl, n-heptyl, and n-octyl groups.
These alkyl groups may optionally be substituted with one to four substituents selected from halogen atoms, lower alkoxycarbonyl, lower alkoxy, optionally substituted aryloxy, optionally substituted cycloalkyl, optionally substituted aryl, or optionally substituted heterocyclic groups.
The halogen atoms as used herein may include fluorine, chlorine, bromine, and iodine atoms. In the following description, the halogen atoms have the same meaning as described above.
The lower alkoxycarbonyl groups may include, for example, straight-chain or branched C
1
-C
6
alkoxycarbonyl groups such as methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, n-pentyloxycarbonyl, neopentyloxycarbonyl, and n-hexyloxycarbonyl groups.
The lower alkoxy groups may include, for example, straight-chain or branched C
1
-C
6
alkoxy groups such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, n-pentyloxy, neopentyloxy, and n-hexyloxy groups. In the following description, the lower alkoxy groups have the same meaning as described above.
The optionally substituted aryloxy groups may include, for example, phenoxy, 1-naphthyloxy, and 2-naphthyloxy groups.
The optionally substituted cycloalkyl groups may include, for example, cyclic C
3
-C
8
alkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl groups.
The optionally substituted aryl groups may include, for example, phenyl and naphthyl groups.
The optionally substituted heterocyclic groups may include, for example, monovalent groups of heterocycles containing one to three heteroatoms, such as furan, tetrahydrofuran, benzo[b]furan, pyrrole, pyrrolidine, pyridine, indole, imidazole, thiophene, and benzo[b]thiophene.
These aryloxy, cycloalkyl, aryl, and heterocyclic groups may optionally be further substituted with one to three substituents selected from halogen atoms, nitro, trifluoromethyl, lower alkyl, or lower alkoxy groups.
The lower alkyl groups as used herein may include, for example, straight-chain or branched C
1
-C
6
alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, neopentyl, and n-hexyl groups.
In the following description, the optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aryloxy, or optionally substituted heterocyclic groups have the same meaning as described above.
When the lower alkyl group in the substituent R
1
is a methyl or ethyl group, it preferably has at least one substituent selected from halogen atoms, lower alkoxycarbonyl, lower alkoxy, optionally substituted aryloxy, optionally substituted cycloalkyl, optionally substituted aryl, or optionally substituted heterocyclic groups.
The optionally substituted lower alkenyl group in the substituent R
1
may include, for example, straight-chain or branched C
2
-C
6
alkenyl groups such as vinyl, 1-methylvinyl, 1-propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 3-methyl-2-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-methyl-2-pent

Affiliated with

Also associated with

Rating

Method for purifying pyruvic acid compounds does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Method for purifying pyruvic acid compounds, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for purifying pyruvic acid compounds will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2938282