Continuous process for the production of optically pure...

Details Continuous process for the production of optically pure... Continuous process for the production of optically pure...

2001-01-22

2002-08-06

Owens, Amelia (Department: 1625)

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

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

active

06429319

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a process for the production of optically pure (S)-beta-hydroxy-gamma-butyrolactone in a continuous manner. More particularly, the present invention relates to a continuous process for the production of optically pure (S)-beta-hydroxy-gamma-butyrolactone by hydrogenation of substituted carboxylic acid derivatives in a fixed-bed reactor which is filled with a catalyst comprising a noble metal and a support.
2. Description of the Prior Art
Optically pure, substituted gamma-butyrolactone is used as an intermediate for the synthesis of a variety of compounds, including medicines such as L-carnitine and ECHB (ethyl (S)-4-cyano-3-hydroxybutyrate), agricultural chemicals, chemical seasonings, and flavorings (U.S. Pat. No. 5,473,104).
Synthesis processes of (S)-&bgr;-hydroxy-&ggr;-butyrolactone can be found in many patents. For example, U.S. Pat. Nos. 5,292,939, 5,319,110 and 5,374,773 disclose preparation method of substituted gamma-butyrolactone by the oxidation of water-soluble hydrocarbons. This process, however, is disadvantageous in that the heat of reaction is too great to conduct the oxidation in high concentrations of the reactant. No separation processes, except chromatography, are described in the above patents. Also, nowhere are mentioned yields. Thus, the processes disclosed in the above patents are not suitable for use in the industrial production.
There are reported multi-step processes for preparing gamma-butyrolactone using L-malic acid or L-aspartic acid as a starting material (J. Org. Chem. 1981, 46, 4319; Synth, Commun. 1986, 16, 183). They, however, have a drawback in that optical activity of intermediates is not maintained during the reaction, in addition to being unsuitable for large-scale production.
Starting from (S)-malic acid ester derivatives, a reducing process for preparing gamma-butyrolactone by use of borane-dimethylsulfide and sodium borohydride has been reported (Chem. Lett. 1984, 1389). However, this process is of a batch type with high production costs and being difficult to apply for industrial production. In addition, the reducing process produces wastes in large quantities, which are detrimental to the environment.
A process disclosed in U.S. Pat. No. 5,808,107 is to prepare optically active (S)-beta-hydroxy-gamma-butyrolactone by reducing L-malic acid dimethyl ester with lithium chloride and sodium borohydride to give (S)-3,4-dihydroxybutyric acid, and treating the intermediate with HCl in a methanol solution. However, this process suffers from the disadvantage of being performed in a complicated batch type manner and brings about pollution of the environment. In addition, the use of sodium borohydride, an expensive and explosive reducing agent, increases the production cost and thus is not suitable for large-scale production. When being used in large quantities, ether employed as a reaction solvent may create a noxious effect on the body owing to its narcotic nature and has the danger of exploding.
In U.S. Pat. No. 5,998,633 is described a process for the preparation of substituted gamma-butyrolactone, in which a hydrocarbon is oxidized to give acetonide, followed by the treatment of the intermediate with an inorganic acid (aqueous HCl solution). This process is also industrially disadvantageous in that it is complicated and produces waste in large quantities.
As described above, the conventional processes are of batch types employing liquid or solid oxidizing or reducing reagents, so that they have the disadvantage of low productivity as well as the production of waste in large quantities. Furthermore, the conventional processes are limited in industrial applications since the low production yield is obtained owing to the complexity thereof.
SUMMARY OF THE INVENTION
Leading to the present invention, the intensive and thorough research on the production of optically active (S)-beta-hydroxy-gamma-butyrolactone, conducted by the present inventors, resulted in the finding that a catalyst, having as a catalytic ingredient a noble metal impregnated in an inorganic oxide support, for hydrogenating optically active, substituted carboxylic acid derivatives is very useful in synthesizing optically pure (S)-beta-hydroxy-gamma-butyrolactone and a fixed bed of the catalyst makes it possible to produce the compound of interest in a continuous manner.
Therefore, it is an object of the present invention to provide a process for the production of optically pure (S)-beta-hydroxy-gamma-butyrolactone from substituted carboxylic acid derivatives, which is improved in the production yield, friendly to the environment, and simple.
Based on the present invention, the above object could be accomplished by a provision of a method for producing optically pure (S)-beta-hydroxy-gamma-butyrolactone from a substituted carboxylic acid derivative by hydrogenation, in which a solution containing 1 to 50% by weight of the substituted carboxylic acid derivative is fed at a WHSV of 0.1 to 10 h
−1
, to a fixed bed reactor which is filled with a catalyst and maintained at a reaction temperature of 50 to 550° C. under a hydrogen partial pressure of 15 to 5,500 psig, said catalyst having a noble metal as a catalytically effective ingredient and an inorganic oxide as a support, said hydrogen being maintained at a molar ratio of 1:1 to 10:1 relative to the substituted carboxylic acid derivative.


REFERENCES:
patent: 5292939 (1994-03-01), Hollingsworth
patent: 5319110 (1994-06-01), Hollingsworth
patent: 5374773 (1994-12-01), Hollingsworth
patent: 5473104 (1995-12-01), McCarthy
patent: 5808107 (1998-09-01), Hollingsworth
patent: 5998633 (1999-12-01), Jacks et al.

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