Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Reexamination Certificate
2000-01-05
2001-07-10
Barts, Samuel (Department: 1623)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
C560S121000, C560S122000, C560S123000, C560S124000, C560S254000
Reexamination Certificate
active
06258975
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a process for producing an optically active 2-hydroxy-4-arylbutyric acid or its ester, an intermediate for synthesis of enalapryl or cilazapryl which is known as an excellent anti-hypertensive agent. The present invention further relates to a process for producing an optically active 2-hydroxy-4-phenylbutyric acid or its ester.
2. Description of the Prior Art
Known processes for producing an optically active 2-hydroxy-4-phenylbutyric acid include:
(i) a process in which racemic 2-hydroxy-4-phenylbutyric acid is used as a starting material and is subjected to an enzymatic reaction in the presence of an acylating agent to obtain the (R)-isomer (Agric. Biol. Chem., 55, 293, 1991),
(ii) a process in which racemic 2-hydroxy-4-phenylbutyric acid is formed into a salt with an optically active amine, and this salt is resolved using a difference in solubility in a diastereomer (EP 329,156),
(iii) a process in which 2-oxo-4-phenylbutyric acid is asymmetrically reduced through an enzymatic reaction [J. Biotechnol., 24, 315 (1992)],
(iv) a process in which 2-oxo-4-phenylbutyric acid is asymmetrically hydrogenated [Std. Surf. Sci. Catal., 78, 139 (1993)],
(v) a process in which D-homophenylalanine is reacted with nitrous acid to form (R)-2-hydroxy-4-phenylbutyric acid (U.S. Pat. No. 5,225,408),
(vi) a process in which benzalpyruvic acid is formed into (R)-2-hydroxy-4-phenyl-3-butenic acid using an L-proline-sodium boron hydride composite, and this butenic acid is then catalytically hydrogenated to form (R)-2-hydroxy-4-phenylbutyric acid [Japanese Laid-Open Patent Application (Kokai) No. 18,050/1992],
(vii) a process in which a racemic 2-hydroxy-4-phenylbutyric acid ester is subjected to an enzymatic reaction to hydrolyze the (S)-isomer alone and obtain an ester of the (R)-isomer [Japanese Laid-Open Patent Application (Kokai) No. 225,499/1989],
(viii) a process in which a racemic 2-acyloxy-4-phenylbutyric acid ester is subjected to an enzymatic reaction to deacylate the (R)-isomer alone and obtain the (R)-hydroxy compound [Japanese Laid-Open Patent Application (Kokai) No. 247,100/1989],
(ix) a process in which a 2-oxo-4-phenylbutyric acid ester is asymmetrically reduced through an enzymatic reaction [Japanese Laid-Open Patent Application (Kokai) No. 328,984/1993],
(x) a process in which racemic 2-hydroxy-4-phenylbutyric acid is optically resolved and then esterified [J. Chem. Soc., Perkin Trans. 1, 1011 (1986)],
(xi) a process in which a 1-menthol ester of 2-oxo-4-phenylbutyric acid is synthesized, and then reduced [Tetrahedron Lett., 423 (1988)], and
(xii) a process in which a 2-oxo-4-phenylbutyric acid ester is asymmetrically hydrogenated (EP 206,993 and EP 564,406).
However, the processes (i), (ii), (vii), (viii) and (x) using the racemic 2-hydroxy-4-phenylbutyric acid ester as a starting material are problematic in that the yield does not exceed 50%. Further, in the processes (iii), (iv), (ix), (xi) and (xii) using 2-oxo-4-phenylbutyric acid or its ester as a starting material, a step of forming the 2-oxo-4-phenylbutyric acid ester is intricate, and the yield is not satisfactory. In the process (v) using D-homophenylalanine as a starting material, the amino acid is itself not a natural-type amino acid, and therefore its production cost is high. Thus, this process is not practical.
Still further, since the process (vi) using benzalpyruvic acid as a starting material comprises two steps, it is intricate and entails a high cost.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide an industrially practical process for producing an optically active 2-hydroxy-4-arylbutyric acid or its ester.
It has now been found that when an optically active acyloxysuccinic anhydride, which can easily be formed from optically active malic acid, is used as a starting material and is reacted with an aromatic compound in the presence of a Lewis acid as a catalyst, an optically active 2-acyloxy-4-oxo-4-arylbutyric acid which is a useful intermediate of an optically active 2-hydroxy-4-arylbutyric acid or its ester can easily be obtained. When this compound is further subjected to reduction, deacylation and esterification in this order, the above-mentioned problems can be solved.
Therefore, the present invention first relates to a process for producing an optically active 2-acyloxy-4-oxo-4-arylbutyric acid of formula (II):
wherein:
R
1
represents a linear, branched or cyclic aliphatic acyl group having from 2 to 7 carbon atoms, which group is unsubstituted or substituted with a halogen atom, or is an aromatic acyl group having from 7 to 11 carbon atoms,
R
2
represents a substituted or unsubstituted aryl group, including a heteroaryl group, having from 4 to 12 carbon atoms, and
* represents an asymmetric carbon atom,
which comprises reacting optically active acyloxysuccinic anhydride of formula (I):
wherein R
1
and * are as defined above, with a substituted or unsubstituted aromatic compound having from 4 to 10 carbon atoms in the presence of a Lewis acid as a catalyst.
The aryl group may be a heteroaryl group which includes, but is not limited to those containing oxygen, nitrogen, and sulfur, for example furan.
The present invention further relates to a process for producing an optically active 2-hydroxy-4-arylbutyric acid of formula (III):
wherein R
2
and * are as defined in formula (II), which comprises subjecting an optically active 2-acyloxy-4-oxo-4-arylbutyric acid of formula (II) to catalytic reduction of the carbonyl group in the 4-position and elimination of the acyl group.
The present invention further relates to a process for producing an optically active 2-hydroxy-4-arylbutyric acid ester of formula (IV):
wherein:
R
2
and * are as defined in formula (II), and
R
3
represents a substituted or unsubstituted linear, branched or cyclic alkyl group having from 1 to 6 carbon atoms, or an aralkyl group having from 7 to 12 carbon atoms,
which comprises subjecting an optically active 2-acyloxy-4-oxo-4-arylbutyric acid of formula (II) to catalytic reduction of the carbonyl group in the 4-position, elimination of the acyl group, and esterification with a substituted or unsubstituted linear, branched or cyclic alkyl alcohol having from 1 to 6 carbon atoms or with an aralkyl alcohol having from 7 to 12 carbon atoms.
The present invention further relates to optically active 2-acyloxy-4-oxo-4-phenylbutyric acid represented by formula (V)
wherein R
1
and * are as defined in formula (II).
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The first process of the present invention is described below.
In this process, optically active acyloxysuccinic anhydride of formula (I) is reacted with an optically substituted aromatic compound having from 4 to 10 carbon atoms in the presence of a Lewis acid as a catalyst to produce an optically active 2-acyloxy-4-oxo-4-arylbutyric acid of formula (II).
The acyl group (R
1
) in the optically active acyloxysuccinic anhydride of formula (I) may be a linear, branched or cyclic aliphatic acyl group having from 2 to 7 carbon atoms, which group is unsubstituted or substituted with a halogen atom or the like, or an aromatic acyl group having from 7 to 11 carbon atoms, such as an acetyl group, a trifluoroacetyl group or a benzoyl group. The acetyl group is industrially preferable in view of post-treatment and cost.
The optically active acyloxysuccinic acid of formula (I) can easily be formed through the reaction of optically active malic acid and halogenated acyl and/or an acid anhydride. For example, optically active acetoxysuccinic anhydride can easily be formed by reacting optically active malic acid with acetic anhydride in the presence of acetyl chloride [J. Org. Chem., 53, 1040 (1988)].
The aromatic compound which is the other starting material for producing the desired optically active 2-acyloxy-4-oxo-4-arylbutyric acid of formula (II) is an aromatic compound in the broad se
Hagiwara Yoshimasa
Izawa Kunisuke
Kurauchi Masahiko
Matsueda Hiroyuki
Nakano Takashi
Ajinomoto Co. Inc.
Barts Samuel
Oblon & Spivak, McClelland, Maier & Neustadt P.C.
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