Process and intermediate products for preparing substantially is

Details Process and intermediate products for preparing substantially is Process and intermediate products for preparing substantially is

1997-10-09

1999-02-09

Geist, Gary

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

Organic compounds

Carboxylic acid esters

560183, C07C 6976, C07C 6973

Patent

active

058697330

DESCRIPTION:

BRIEF SUMMARY
The present invention relates to a process for the preparation of essentially isomerically pure methyl ##STR2## where R is an aromatic radical which is substituted by customary groups and R' is a C.sub.1 -C.sub.3 -alkyl group. are obtained from the corresponding methyl .alpha.-ketoacetates by a reaction similar to the method of Wittig or Wittig-Horner (EP-A 280 185, EP-A 513 580). No information is found in this literature on the preparation of the essentially pure E isomers which are preferred with regard to their biological properties.
The prior-art methods have the disadvantage that the triphenyl-phosphine oxide which is formed as a by-product necessitates a purification step which is difficult and complicated on an industrial scale.
It was therefore an object of the present invention to provide a process which yields the essentially pure E isomers of the methyl present invention to provide an economical process for the preparation of these compounds which is simple to carry out on an industrial scale.
Accordingly, we have found that these objects are achieved by a process for the preparation of essentially isomerically pure methyl first converting a suitable methyl ##STR3## with an alkyl metal compound of the formula III ##STR4## subsequently dehydrating IV in the presence of an acid to give a mixture Ia and Ib ##STR5## and, subsequently, converting this mixture in the presence of a base in an inert polar solvent into the essentially isomerically pure methyl
In the process according to the invention, the procedure is generally followed in which a suitable methyl converted with an alkyl metal compound of the formula III into the of the formula IV ##STR6## M in formula III is a metal ion equivalent. Suitable metal ions are, for example, ions of transition metals or of alkaline earth metals such as tin, magnesium, zinc, cadmium or mercury. Particularly preferred substances are alkyl tin halides, alkylmagnesium halides (for example ethylmagnesium chloride or ethylmagnesium bromide), ethylzinc chloride, ethylzinc bromide, ethylzinc iodide or diethylzinc.
This reaction is conventionally carried out at from -80.degree. C. to 100.degree. C., preferably -20.degree. C. to 80.degree. C.
Suitable solvents or diluents are aliphatic hydrocarbons such as pentane, hexane, cyclohexane and petroleum ether, aromatic hydrocarbons such as toluene, o-, m- and p-xylene, ethers such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, acetals such as formaldehyde dimethyl acetal and acetone dimethyl ketal, particularly preferably tetrahydrofuran, diethyl ether, diisopropyl ether, tertbutyl methyl ether, formaldehyde dimethyl acetal and acetone dimethyl ketal. Mixtures of the abovementioned solvents can also be used.
The alkyl metal compounds are generally employed in at least equimolar amounts. However, to increase the yield it is advantageous to employ the alkyl compounds III in an excess of from 500 mol % to 100 mol %, preferably 300 mol % to 150 mol %, especially 200 mol % to 100 mol %, the formula II.
The reaction is advantageously carried out in such a way that the alkyl metal compound is taken up in a solvent or diluent and the resulting mixture is treated with the .alpha.-ketoester II, a little at a time, with cooling. After all of the ketoester II has been added, the reaction mixture is heated to approximately 25.degree. C. (room temperature). The course of the reaction can be monitored chromatographically. After the reaction has ended, working-up of the reaction mixture is conventionally carried out in such a way that the mixture is first hydrolyzed with a dilute aqueous acid or water and subsequently extracted using an organic solvent.
The literature cited at the outset discloses the starting materials II which are required for the preparation of the compounds I. The alkyl metal compounds are also known (Houben-Weyl, Vol. 13/2, pp. 53 et seq. and pp. 570 et seq.) or can be prepared by following the literature cited. of the formula IV can be converted, without further pu

REFERENCES:
patent: 4937372 (1990-06-01), Wenderoth et al.
patent: 5298527 (1994-03-01), Grammenos et al.

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