Title of Invention	"PROCESS FOR PREPARING QUINOLONE-AND NAPHTHYRIDONECARBOXYLIC ACIDS AND ESTERS THEREOF"
Abstract	1. Process for preparing quinolone- and naphthyndonecarboxylic acids and es¬ters thereof of the formula (I) in which R1, R2, R3, R4, R5, Y and A are as described in the specification.

Full Text

The present invention relates to an improved process for preparing quinolone- and naphthyridonecarboxylic acids and esters thereof starting from benzoyl chlorides and nicotinoyl chlorides, respectively. Quinolone- and naphthyridonecarboxylic acids and esters thereof are intermediates for preparing known, pharmaceutically active quinolonecarboxylic acids and naphthyridonecarboxylic acids, respectively. EP-A-300 311 discloses a preparation of quinolonecarboxylic acids where a benzoyl chloride is acylated with an aminoacrylic ester, an amine exchange is carried out with the aroylacrylic ester, the resulting aminoacrylate is cyclized, the resulting ester is hydrolyzed and the resulting quinolonecarboxylic acid is precipitated out by addition of an acid. Here, the yields are between 71 and 79%. The solvents which are given for the individual reaction steps are: for the acylation toluene, xylene, cyclohexane, open-chain hydrocarbons, DMF and DMSO, for the amine exchange additionally alcohols and butyl glycol and for the cyclization only higher alcohols, amino alcohols, DM1;, DMSO, dioxane and N-methylpyrrolidone. If non-polar to slightly polar solvents, for example hydrocarbons, are to be employed for the acylation and the amine exchange, a different, polar, optionally even protic solvent, tor example butyl alcohol, has to be employed for the cyclization. To carry out the entire reaction in only one solvent seems possible only in a strongly polar solvent, for example DMF or DMSO. In all examples of EP-A 300 311, the solvent was changed, namely from the non-polar aprotic toluene or cyclohexane for the first and, if appropriate, the second step to the polar, protic butyl glycol for the third and, if appropriate, second step. The change ol solvent leads to considerable expense for the separate removal of two different solvents, for drying the intermediate at whose stage the solvent exchange is carried out and for disposal or regeneration of two different solvents. Moreover, the yields which can he obtained are still not entirely satisfactory. According to HP-A 176 846, for reacting a benzoyl halide with an acrylic acid derivative ( acylation), use is made of methylene chloride, chloroform, toluene, tetra-hydrofuran or dioxane. In Liebigs Ann Chern. 1_987, 29-37, a dipolar aprotic solvent, for example DMF, DMSO or N-methylpyrrolidone, is specified for the cyclocondensation of 3-amino-2-ben/.oylacrylic esters to 4-quinolone-3-carboxylic esters (:= cyclization). Thus, there is a general bias in the art against using a non-polar to slightly polar solvent for the entire reaction sequence. This invention, accordingly, provides a process for preparing quinolone- and naph-thyridonecarboxylic acids and esters thereof of the formula (I) (FigureRemoved) in which R1 represents hydrogen or C ] -Chalky 1, R*- represents halogen, R^ represents halogen, R4 represents hydrogen, halogen or nitro, Y represents C,-C6-alkyl, 2-fluoroethyl, cyclopropyl, fluorocyclopropyl, iso-propyl, 4-fluorophenyl or 2,4-difluorophenyl and A represents nitrogen or C-R^ where R^ = hydrogen, methyl, methoxy, halogen, nitro or cyano, where Y and R5 together may also represent -CH2-CH2-O- or -CH(CH3)-CH2-O-, where the terminal CH2- or the CH(CH3)- group is attached to the nitrogen atom, characteri/ed in that a) a benzoyl or nicotinoyl chloride of the formula (II) (FigureRemoved) in which R2, R3, R4 an R" represents halogen, is reacted in the presence of a base with an aminoacrylic ester of the formula (III) CH— COOR1 II 1? CH— NZ1Z2 in which R ' represents C ] -C4-alkyl and Z ' and Z2 independently of one another each represent C ] -C4-alkyl or together with the linking nitrogen atom form a 5- to 6-membered saturated or unsaturated ring which may optionally contain up to two further hetero groups selected from the group consisting of O atoms, S atoms and SC>2 groups, thus giving a (Het)-aroylacrylic ester of the formula (IV) COOR1 (IV), 2' "A Ru NZ'Z in which (FigureRemoved) RI represents C i -C^alkyl and R2, R^, R4 ancj A are each as defined under formula (I), R.6 is as defined under formula (II) and /' and /2 are each as defined under formula (III), h) the (I let)-aroylacrylic ester of the formula (IV) is subjected to an amine exchange with an amine of the formula (V) H2N-Y (V), in which Y is as defined under (I), thus giving a (Het)-aroylacrylic ester of the formula (VI) (FigureRemoved) in which R' represents C j -C4-alkyl and RA R.3, R4, Y and A are each as defined under formula (I) and R() is as defined under formula (II), c) the (Het)-aroylacrylic ester of the formula (VI) is cyclized in the presence of a base, thus giving a quinolone or naphthyridone ester of the formula (I) in which R' represents Cj-C^alkyl and d) if a quinolone- or naphthyridonecarboxylic acid of the formula (1) is to be prepared in which R' represents hydrogen, the ester which is present after step c) is hydrolyzed and the acid of the formula (I) in which R! represents hydrogen is isolated after addition of an acid, where the intermediates of the formulae (IV) and (VI) are not isolated and steps a) to c) are carried out in the presence of the same, non-polar to slightly polar solvent. The symbols used in the formulae (I) to (VI) preferably have the following meanings: if R' represents Cj-C^alkyl: methyl or ethyl. R.2; chlorine or fluorine. R.3; fluorine. R.4; hydrogen, chlorine, fluorine or nitro. R": fluorine or chlorine. A: C-R^ where R^ = hydrogen, methyl, methoxy, halogen or cyano or N. Y: ethyl, cyclopropyl, fluorocyclopropyl, 2,4-difluorophenyl or together with R^ -CH(CH3)-CH2-O-. /^ and Z^: methyl or ethyl. Suitable reaction temperatures for step a) are, for example, in the range from 25 to 120°C. Preference is given to carrying out the reaction at from 30 to 80°C. Suitable bases for step a) are, for example, tertiary amines, like those of the formulae N(R7)3 R—N N-R7 , R7—N 0 or V R/ R7 -7- in which R? represents C]-C]4-alkyl or benzyl. If a plurality of R? groups is present in a molecule, these may be identical or different. R? preferably represents Cj-C^alkyl. A particularly preferred tertiary amine is triethylarnine. In step a), in general at least one equivalent of base is employed per mole of the acyl chloride of the formula (II). This amount is preferably from 1 to 2 equivalents. Greater amounts are not critical, but uneconomical. Hydrochloride of the base employed which precipitates out during the reaction can, if required, be removed mechanically (for example by filtration) or by extraction with water. Preferably, this hydrochloride is not separated off. Suitable reaction temperatures for step b) are, for example, in the range from 5 to 1()0°C. Preference is given to carrying out the reaction at from 10 to 80°C. Preferred amines of the formula (V) are ethylamine, cyclopropylamine, 2,4-difluoroaniline, aminopropanol and fluorocyclopropylamine. In step b) in general at least one equivalent of amine is employed per mole of ester of the formula (IV). This amount is preferably from 1 to 1.3 equivalents. Greater amounts are not critical, but uneconomical. The liberated dialkvlamine, preferably dimethyl- or diethylamine, is preferably removed from the reaction mixture, for example by adding an equivalent of acid and mechanical removal, for example by filtration, or by extraction with water. If appropriate, the hydrochloride produced in step a) can also be separated off here. The liberated dialkvlamine can also be removed from the reaction mixture by distillative removal at low temperatures, for example. Suitable reaction temperatures for step c) are, for example, in the range from 50 to 200°C. The respective optimum reaction temperature depends on the substitution pattern and can easily be determined by routine preliminary experiments. Suitable bases for step c) are, for example, potassium carbonate, sodium carbonate, sodium hydride and sodium tert-butoxide. Preference is given to potassium carbonate. Based on 1 mol of the compound of the formula (VI), it is possible to employ, for example, from 1 to 4 molar equivalents of the base. This amount is preferably from 1.1 to 1.5 molar equivalents. When using potassium carbonate or sodium carbonate, it is advantageous to remove the water of reaction which is liberated, for example using a water separator. Step c) can, if appropriate, be carried out in the presence of a phase-transfer catalyst. Suitable phase-transfer catalysts are, for example, tetraalkylammonium halides. The ester of the formula (1) where Ri = Cj-C4-alkyl can be isolated, for example, as follows: initially, a fraction of the solvent is distilled off, for example from 40 to 60% by weight, water is then added, upon which in general the ester begins to precipitate out, the remaining solvent is then distilled off and the ester is then separated off, for example, by filtration, washed with an alcohol, for example a Cj-C^alkyl alcohol, and subsequently dried under reduced pressure. The ester hydrolysis for preparing acids of the formula (I) where R! = hydrogen from esters of the formula (I) where R! = Cj-C^alkyl can be carried out by customary methods in an acidic or in an alkali medium. If the esters in question are base-sensitive esters of the formula (I), preference is, of course, given to hydrolyzing the esters in an acidic medium. For separating off and isolating acids of the formula (I), it is possible to add, for example, acetic acid, sulphuric acid or hydrochloric acid. The precipitated acid can be separated off, for example, by filtration. It is an essential feature of the process according to the invention that the intermediates of the formulae (IV) and (VI) obtained after carrying out steps a) and b) are not isolated. It is another essential feature of the process according to the invention that steps a) to c) are carried out without solvent exchange in the same, non-polar to slightly polar solvent. Suitable solvents are, for example, alkylbenzenes, in particular those containing from 1 to 3 Ci-C4-alkyl groups per molecule, halogenobenzenes, in particular those containing from 1 to 2 halogen atoms, preferably chlorine atoms, per molecule, halo-genoalkylbenz.enes, in particular those containing from 1 to 2 halogen atoms, preferably chlorine atoms, and from 1 to 2 Ci-C4-alkyl groups per molecule, alicyclic hydrocarbons, and particularly those which contain from 5 to 7 ring carbon atoms and which arc optionally substituted with from 1 to 2 C]-C4-alkyl groups, open-chain, saturated or unsaturated hydrocarbons, in particular those which are straight-chain or branched and contain from 5 to 18 carbon atoms, and any mixtures of such solvents. Care should be taken to choose those solvents whose boiling point at atmospheric pressure is above the intended reaction temperature or, in the case of reaction temperatures above the boiling point of the intended solvent at atmospheric pressure, to use pressure-proofed, closed apparatuses. If the boiling point of the solvent at atmospheric pressure exceeds the intended reaction temperature substantially, it is also possible to operate under reduced pressure. Particular examples of solvents are: toluene, xylenes, mesitylene, ethylbenzene, di-ethylben/enes, isopropylben/ene, chlorobenzene, dichlorobenzenes, chlorotoluenes, cyclohexane and hydrocarbon mixtures which contain at least 80% by weight of one or more straight-chain or branched €5- to C ^-hydrocarbons. Preferred solvents are toluene, xylenes, mesitylene, isopropylbenzene, chlorobenzene and dichlorobcnzenes. It is possible to use, for example, from 300 to 1000 ml of solvent per mole of acyl chloride of the formula (II). This amount is preferably from 400 to 800 ml. Greater amounts of solvent are not critical, but uneconomical. The process according to the invention has the advantages that three reaction steps can be carried out without isolating the intermediates and without changing the solvent, and that higher yields than in the prior art are obtained. The yields which can be obtained are above 80% of theory, frequently above 85% of theory. This means that the process according to the invention can be carried out in a technically simple manner and particularly effectively, since the expenditure for the removal and disposal or regeneration of a second solvent and for the isolation and drying of intermediates is not incurred, and it is still possible to obtain higher yields than hitherto. These obtainable advantages are extremely surprising, because hitherto the use of polar solvents had been thought to be central, at least for the cyclization reaction (step c). Particularly preferred compounds which can be prepared by the process according to the invention from the corresponding compounds of the formulae (II), (III) and (V) are the following: l-cyclopropyl-7-chloro-6-fluoro-l,4-dihydro-4-oxo-3-quinoline-carboxylic acid, ethyl l-cyclopropyl-6,7,8-trifluoro-l,4-dihydro-4-oxo-3-quinoline-carboxylate, ethyl l-cyclopropyl-6,7-difluoro-l,4-dihydro-4-oxo-3-quinoline-carboxylate, ethyl 1 -cyclopropyl-6,7-difluoro-8-methoxy-l ,4-dihydro-4-oxo-3-quinoline-carb- oxylate. ethyl 1 -cyclopropyl-6,7-difluoro-8-cyano-l ,4-dihydro-4-oxo-3-quinolinecarboxylate, ethyl 1 -(2-fluoro)cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinoline-carb- oxylate, ethyl 1 -cyclopropyl-8-chloro-6,7-difluoro-l ,4-dihydro-4-oxo-3-quinoline-carb- oxylate, ethyl 1 -ethyl-6,7,8-trittuoro-1,4-dihydro-4-oxo-3-quinoline-carboxylate, ethyl 7-chloro-1 -(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyri- done-3-carboxylale, ethyl 7-chloro- l-cyclopropyl-6-fluoro-l,4-dihydro-4-oxo-l,8-naphthyridone-3- carboxylate, ethyl 1 -cyclopropyl-7-chloro-6-fluoro-l ,4-dihydro-4-oxo-3-quinoline-carboxylate and ethy 1 9,1 O-difluoro-2,3 -dihydro-3 -methy I-7-oxo-7H-pyrido( 1,2,3 -de)( 1,4)benzox- azine-6-carboxylate. A specific aspect of the present invention is a process for cyclizing a (Het)-aroylacrylic ester of the formula (VI) (FigureRemoved) in which R1 represents C \ -C4~alky 1, I Ry represents halogen, R^ represents hydrogen, halogen or nitro, (VI), R.6 represents halogen, Y represents C j-C^-alkyl, 2-fluoroethyl, cyclopropyl, fluorocyclopropyl, iso-propyl, 4-fluorophenyl or 2,4-difluorophenyl and A represents nitrogen or C-R^ where R^ = hydrogen, methyl, methoxy, halogen, nitro or cyano, where Y and R5 together may also represent -CH2-CH2-O- or -CH(CH3)-CH2-O-, where the terminal CH2- or the CH(CH3)- group is attached to the nitrogen atom, in the presence of a base, forming an ester of the formula (I) (FigureRemoved) in which the symbols used are each as defined above under formula (VI), characterized in that the process is carried out in the presence of a non-polar to slightly polar solvent. This process is described above in more detail. Preferred non-polar to slightly polar solvents are: alkylbenzenes, halogenobenzenes, halogenoalkylben/enes, alicyclic hydrocarbons, open-chain hydrocarbons and any mixtures of such solvents. Examples Example 1 At 70°C, 160 g of 2,4-dichloro-5-iluorobenzoyl chloride were added dropwise over a period of 50 minutes to a solution of 380 g of dichlorobenzene (mixture of isomers), 110 g of ethyl N,N-dimethylaminoacrylate and 77 g of triethylamine. The mixture was subsequently stirred at 70°C for 2 hours and cooled to room temperature. At room temperature, 51 g of acetic acid were added and the mixture was again heated to 70°C. At 7(.)°C, 45 g of cyclopropylamine were then added dropwise, the reaction mixture was subsequently admixed with 100 ml of water and the organic phase that Ibrmed was separated off. The organic phase was metered into a mixture of 59 g of potassium carbonate and 190 g of dichlorobenzene (mixture of isomers) at from 180 to 184°C. The water of reaction which was liberated was separated off via a water separator. After all the water had been separated off, the mixture was cooled to 80°C and, at a pressure of 40 mbar, 340 ml of dichlorobenzene were distilled off. 80 g of 35% strength aqueous sodium hydroxide solution and 350 g of water were then added, and the remaining dichlorobenzene was distilled off. After addition of 180 g of acetic acid and 100 g of water, the product was filtered off with suction and the isolated solid was washed 3 times with 150 ml of water each time and 3 times with 200 ml of isopropanol each time. Drying under reduced pressure at 60°C gave 173 g of l-cyclopropyl-7-chloro-6-fluoro-l,4-dihydro-4-oxo-3-quinoline-carboxylic acid. This corresponds to a yield of 87% of theory. A mixture of 380 g of xylene (mixture of isomers), 110 g of ethyl N,N-dimethylami-noacrylate and 77.4 g of triethylamine was initially charged, and 160 g of 2,4-dicliloro-5-fluorobenzoyl chloride were added dropwise at 70°C over a period of 60 minutes. The mixture was subsequently stirred at 70°C for 2 hours and cooled to room temperature. At room temperature, 51 g of acetic acid were then added, and the mixture was again heated to 70°C. At 70°C, 45 g of cyclopropylamine were then added dropwise. 100ml of water were added to the reaction mixture which was stirred for 15 minutes, and the organic phase that formed was separated off. The organic phase was metered into a mixture of 89 g of potassium carbonate and 190 g of xylene (mixture of isomers) at from 140 to 142°C. The water of reaction that was liberated was separated off via a water separator. After all the water had been separated off, the mixture was cooled to 80°C and, at a pressure of 40 mbar, xylene was distilled off. 80 g of 45% strength aqueous sodium hydroxide solution and 350 g of water were then added, and the remaining xylene was distilled off. After addition of 180 g of acetic acid and 100 g of water, the product was filtered off with suction and the solid was washed 3 times with 150 ml of water each time and 3 times with 200 ml of isopropanol each time. Drying under reduced pressure at 60°C gave 170 g of l-cyclopropyl-7-chloro-6-fluoro-l,4-dihydro-4-oxo-3-quinoline-carboxylic acid. This corresponds to a yield of 86% of theory. Example 3 380 g of chlorobenzene, HOg of ethyl N,N-dimethylaminoacrylate and 77.4 g of triethylamine were initially charged, and 160 g of 2,4-dichloro-5-fluorobenzoyl chloride were added dropwise at 70°C over a period of 60 minutes. The mixture was subsequently stirred at 70°C for 2 hours and then cooled to room temperature. 51 g of acetic acid were then added at room temperature, and the mixture was again heated to 70°C. At 70°(". 45 g of cyclopropylamine were then added dropwise. 100 ml of water were added to the reaction mixture which was stirred for 15 minutes, and the organic phase that formed was separated off. The aqueous phase was extracted with 50 ml of chloroben/ene and the combined organic phases were metered into a mixture of 1 19 g of potassium carbonate, 1 g of tributylammonium bromide and 190 g of chlorobenzene, at 131"C. The water of reaction that was liberated was separated off via a water separator. Alter all the water had been separated off, the mixture was cooled to 20°C and the precipitated solid was filtered off with suction using a nutsche filter. The solid was then washed 3 times with 200 ml of isopropanol each time. Drying under reduced pressure at 60°C gave 186 g of ethyl l-cyclopropyl-7-chloro-6-fluoro-1,4-dihydro-4-oxo-3-quinoline-carboxylate. This corresponds to a yield of 86% of theory. Example 4 At 45°C, 280 g of 2,3,4,5-tetrafluorobenzoyl chloride were added dropwise over a period of 60 minutes to a solution of 270 g of toluene, 189.8 g of ethyl N,N-dimeihylaminoacrylate and 144.2 g of triethylamine. The mixture was subsequently stirred at 50°C for 1 hour and then cooled to room temperature. At room temperature, 95.2 g of acetic acid were then added, and 75.2 g of cyclopropylamine were then added dropwise at from 20 to 30°C. 200 ml of water were then added to the reaction mixture, and the organic phase that formed was separated off. The aqueous phase was extracted with 82 g of toluene and the combined organic phases were metered into a mixture of 110 g of potassium carbonate and 404 g of toluene, at 111°C. The water of reaction that was liberated was separated off via a water separator. After all the water had been separated off, the mixture was cooled to 60°C and 1280 g of water were added. At a temperature of 40°C and a pressure of 100 mbar, the toluene was distilled off. The suspension was cooled to 20°C and filtered off with suction using a nutsche filter. The solid was then washed 3 times with 200 ml of water each time and 3 times with 250 ml of isopropanol each time and subsequently dried at 50°C under reduced pressure. This gave 374 g of ethyl l-cyclopropyl-6,7,8-trifluoro-l,4-dihydro-4-oxo-3-quinoline-carboxylate. This corresponds to a yield of 91%o!'theor>. Examplc 5 At 45°C, 140 g of 2,3,4,5-tetrafluorobenzoyl chloride were added dropwise over a period of 60 minutes to a solution of 202 g of toluene, 94.9 g of ethyl N,N-dimethylaminoacrylate and 72.1 g of triethylamine. The mixture was subsequently stirred at 43°C for 1 hour and then cooled to room temperature. 37.6 g of cyclopropylamme were then added dropwise at from 20 to 30°C, and the mixture was stirred for 1 hour. The dimethylamine was subsequently distilled off at a pressure of 80 mbar. 100 ml of water were added to the reaction mixture, and the organic phase that formed was separated off. The aqueous phase was extracted with 41 g of toluene and the combined organic phases were metered into a mixture of 55 g of potassium carbonate and 202 g of toluene, at 110°C. The water of reaction that was liberated was separated off via a water separator. After all the water had been separated off, the mixture was cooled to 60°C and 640 g of water were added. At a temperature of 40°C and a pressure of 100 mbar, the toluene was distilled off. The suspension was cooled to 20°C and filtered off with suction using a nutsche filter. The resulting solid was washed 3 times with 150 ml of water each time and 3 times with 150 ml of iso-propanol each time and subsequently dried under reduced pressure at 50°C. This gave 172 g of ethyl l-cyclopropyl-6,7,8-trifluoro-l,4-dihydro-4-oxo-3-quinoline-carboxylate. This corresponds to a yield of 84% of theory. Example 6 Example 2 was repeated, but isopropylbenzene was used instead of xylene, and the cycli/ation was carried out at from 156 to 158°C. Drying under reduced pressure at 60°C gave 177g of l-cyclopropyl-7-chloro-6-fluoro-l,4-dihydro-4-oxo-3-quinoline-earboxylie acid. This corresponds to a yield of 89% of theory. Examplc 7 Example 2 was repeated, but mesitylene was used instead of xylene, and the cycli-zation was carried out at from 166 to 168°C. Drying under reduced pressure at 60°C gave 174 g of l-cyclopropyl-7-chloro-6-fluoro-l,4-dihydro-4-oxo-3-quinoline-carboxylic acid. This corresponds to a yield of 88% of theory. Example 8 272 g of toluene, 111 g of ethyl N,N-dimethylaminoacrylate and 85 g of triethyl-amine were initially charged, and 156g of 2,4,5-trifluorobenzoyl chloride were added dropwise at from 50 to 55°C over a period of 60 minutes. The mixture was subsequently stirred at 55°C for 2 hours and then cooled to room temperature. 56 g of acetic acid were then added, and 48.6 g of cyclopropylamine were added dropwise at irom 20 to 30°C. 250 ml of water were then added to the reaction mixture which was stirred lor 15 minutes, and the organic phase was separated off. The organic phase was metered into a mixture of 65 g of potassium carbonate and 240 g of toluene, at 110°C. The water of reaction that was liberated was separated off via a water separator. After all the water had been separated off, the mixture was cooled to 30°C, and 500 ml of water were added. At a pressure of from 120 to 180 mbar, the toluene was distilled off. The mixture was subsequently cooled to 20°C and the product was filtered off with suction. The isolated solid was washed three times with 100 ml of water each time and three times with 100 ml of isopropanol each time. Drying under reduced pressure at 50°C gave 206 g of ethyl l-cyclopropyl-6,7-difluoro-l,4-di-hydro-4-oxo-3-quinoline-carboxylate. This corresponds to a yield of 88% of theory. We claim: I. Process for preparing quinolone- and naphthyridonecarboxylic acids and es¬ters thereof of the formula (I) (Formula Removed) in which R1 represents hydrogen or C1 -C4-alkyl, R2 represents halogen, R3 represents halogen, R4 represents hydrogen, halogen or nitro, Y represents C1-C6-alkyl, 2-fluoroethyl, cyclopropyl, fluorocyclo-propyl, isopropyl, 4-fluorophenyl or 2,4-difiuorophenyl and A represents nitrogen or C-R5 where R5 = hydrogen, methyl, methoxy, halogen, nitro or cyano, where Y and R5 together may also represent -CH2-CH2-O- or -CH(CH3)-CH2-0-, where the terminal CH - or the CH(CH3)- group is at¬tached to the nitrogen atom, characterized in that a) from 25 to 120°C a benzoyl or nicotinoyl chloride of the formula (II) v (Formula Removed) in which R2, R3, R4 And A are each as defined under formula (I) and R6 represents halogen, is reacted in the presence of a tertiary amine as a base with an aminoacrylic ester of the formula (III) (Formula Removed) in which R1 represents C1-C4-alkyl and Z1 and Z2 independently of one another each represent C1-C4-alkyl or together with the linking nitrogen atom form a 5- to 6-mem-bered saturated or unsaturated ring which may optionally con¬tain up to two further hetero groups selected from the group consisting of O atoms, S atoms and SO2 groups, thus giving a (Het)-aroylacrylic ester of the formula (IV) (Formula Removed) in which R1 represents C 1 -C4-alkyl and R2, R3, R4 and A are each as defined under formula (I), R6 is as defined under formula (II) and Z1 and Z2 are each as defined under formula (III), b) from 5 to 100°C the (Het)-aroylacrylic ester of the formula (IV) is subjected to an amine exchange with an amine of the formula of the group ethylamine, cyclopropylamine, 2, 4-difluoroniline, aminopropanol or fluorocyclopropylamine. thus giving a (Het)-aroylacrylic ester of the formula (VI) (Formula Removed) in wliich R1 represents C1-C4-alkyl and R2, R3, R4, Y and A are each as defined under formula (I) and R6 is as defined under formula (IT), c) from 50 to 200°C the (Het)-aroylacrylic ester of the formula (VI) is cyclized in the presence of a base of the group potassium carbonate, sodium carbonate, sodium hydride and sodium tert-butoxide, thus giving a quinolone or naphthyridone ester of the formula (I) in which R1 represents C1-C4-alkyl and d) if a quinolone- or naphthyridonecarboxylic acid of the formula (I) is to be prepared in which R1 represents hydrogen, the ester which is pres¬ent after step c) is hydrolyzed and the acid of the formula (I) in which R1 represents hydrogen is isolated after addition of an acid, where the intermediates of the formulae (IV) and (VI) are not isolated and steps a) to c) are carried out in the presence of the same, non-polar to slightly polar solvent of the group alkylbenzene, halogenobenzene, halogenoalkylbenzene, alicyclic hydrocarbon, open-chain hydrocarbon, or any mixture of these solvents. 2. Process as claimed in Claim 1, wherein the solvent used is toluene, xylene, mesitylene, isopropylbenzene, chlorobenzene or dichlorobenzene. 3. Process as claimed in Claims 1 to 2, wherein from 300 to 1000 ml of solvent are employed per mole of acyl chloride of the formula (II). 4. Process as claimed in Claims 1 to 3, wherein the symbols used in the formulae (I) to (VI) have the following meanings: Rl, insofar as it represents C1-C4alkyl: methyl or ethyl, R2 : chlorine or fluorine, R3: fluorine, R4: hydrogen, chlorine, fluorine or nitro, R5: fluorine or chlorine, A: C-R5 where R5 = hydrogen, methyl, methoxy, halogen or cyano or N, Y: ethyl, cyclopropyl, fluorocyclopropyl, 2,4-difluorophenyl or together with R5 -CH(CH3) -CH2-0- and Z1 and Z2 : methyl or ethyl.

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851-DEL-1999-Abstract-(11-06-2008).pdf

851-del-1999-abstract.pdf

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