2,4-dichloro-3-cyano-5-fluorobenzoyl chloride

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: An alternative process for the preparation of the intermediate compound 2,4-dichloro-3-cyano-5-fluoro-benzoyl chloride, which serves as a starting material for the preparation of 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (EP-A-0 276 700) and which can converted into 3-cyano-2,4,5-trifluoro-benzoyl fluoride, starts from 5-fluoro-1,3-xylene: 5-fluoro-1,3-xylene is dichlorinated in the nucleus under ionic conditions in the presence of a catalyst to give 2,4-dichloro-5-fluoro-1,3-dimethylbenzene and this is then chlorinated under free-radical conditions in the side chains to give 2,4-dichloro-5-fluoro-3-dichloromethyl-1-trichloromethylbenzene. This is hydrolysed via 2,4-dichloro-5-fluoro-3-dichloromethylbenzoic acid to give 2,4-dichloro-5-fluoro-3-formyl-benzoic acid and then reacted to give 2,4-dichloro-5-fluoro-3-N-hydroxyiminomethyl-benzoic acid. By treatment with thionyl chloride, 2,4-dichloro-3-cyano-5-fluoro-benzoyl chloride is obtained, which can additionally be reacted by means of a chlorine/fluorine exchange to give 3-cyano-2,4,5-trifluoro-benzoyl fluoride. ##STR4##

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4100 ml of thionyl chloride and 41 ml of pyridine were introduced into a stirred apparatus fitted with metering device and gas outlet leading to a scrubber via a reflux condenser, and, at 20° C., 2050 g of 3-cyano-2,4-dichloro-5-fluorobenzoic acid (99.5% strength) were introduced at the rate of hydrogen chloride/sulphur dioxide evolution. At the end of the addition, the mixture was heated to reflux until the evolution of gas ceased. The mixture was then distilled. In the boiling range from 142 to 145° C./10 mbar, 2150 g (95.7% of theory) of 3-cyano-2,4-dichloro-5-fluorobenzoyl chloride were obtained (content according to GC: 98.0%). fitted with metering device and gas outlet leading to a scrubber via a reflux condenser At the end of the addition the mixture was heated to reflux until the evolution of gas The mixture was then distilled

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4100 ml of thionyl chloride and 41 ml of pyridine were introduced into a stirred apparatus fitted with metering device and gas outlet leading to a scrubber via a reflux condenser, and, at 20° C., 2050 g of 3-cyano-2,4-dichloro-5-fluorobenzoic acid (99.5% strength) were introduced at the rate of hydrogen chloride/sulphur dioxide evolution. At the end of the addition, the mixture was heated to reflux until the evolution of gas ceased. The mixture was then distilled. In the boiling range from 142 to 145° C./10 mbar, 2150 g (95.7% of theory) of 3-cyano-2,4-dichloro-5-fluorobenzoyl chloride were obtained (content according to GC: 98.0%). fitted with metering device and gas outlet leading to a scrubber via a reflux condenser At the end of the addition the mixture was heated to reflux until the evolution of gas The mixture was then distilled

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: An alternative process for the preparation of the intermediate compound 2,4-dichloro-3-cyano-5-fluoro-benzoyl chloride, which serves as a starting material for the preparation of 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (EP-A-0 276 700) and which can converted into 3-cyano-2,4,5-trifluoro-benzoyl fluoride, starts from 5-fluoro-1,3-xylene: 5-fluoro-1,3-xylene is dichlorinated in the nucleus under ionic conditions in the presence of a catalyst to give 2,4-dichloro-5-fluoro-1,3-dimethylbenzene and this is then chlorinated under free-radical conditions in the side chains to give 2,4-dichloro-5-fluoro-3-dichloromethyl-1-trichloromethylbenzene. This is hydrolysed via 2,4-dichloro-5-fluoro-3-dichloromethylbenzoic acid to give 2,4-dichloro-5-fluoro-3-formyl-benzoic acid and then reacted to give 2,4-dichloro-5-fluoro-3-N-hydroxyiminomethyl-benzoic acid. By treatment with thionyl chloride, 2,4-dichloro-3-cyano-5-fluoro-benzoyl chloride is obtained, which can additionally be reacted by means of a chlorine/fluorine exchange to give 3-cyano-2,4,5-trifluoro-benzoyl fluoride. ##STR4##

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: An alternative process for the preparation of the intermediate compound 2,4-dichloro-3-cyano-5-fluoro-benzoyl chloride, which serves as a starting material for the preparation of 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (EP-A-0 276 700) and which can converted into 3-cyano-2,4,5-trifluoro-benzoyl fluoride, starts from 5-fluoro-1,3-xylene: 5-fluoro-1,3-xylene is dichlorinated in the nucleus under ionic conditions in the presence of a catalyst to give 2,4-dichloro-5-fluoro-1,3-dimethylbenzene and this is then chlorinated under free-radical conditions in the side chains to give 2,4-dichloro-5-fluoro-3-dichloromethyl-1-trichloromethylbenzene. This is hydrolysed via 2,4-dichloro-5-fluoro-3-dichloromethylbenzoic acid to give 2,4-dichloro-5-fluoro-3-formyl-benzoic acid and then reacted to give 2,4-dichloro-5-fluoro-3-N-hydroxyiminomethyl-benzoic acid. By treatment with thionyl chloride, 2,4-dichloro-3-cyano-5-fluoro-benzoyl chloride is obtained, which can additionally be reacted by means of a chlorine/fluorine exchange to give 3-cyano-2,4,5-trifluoro-benzoyl fluoride. ##STR4##

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4100 ml of thionyl chloride and 41 ml of pyridine were introduced into a stirred apparatus fitted with metering device and gas outlet leading to a scrubber via a reflux condenser, and, at 20° C., 2050 g of 3-cyano-2,4-dichloro-5-fluorobenzoic acid (99.5% strength) were introduced at the rate of hydrogen chloride/sulphur dioxide evolution. At the end of the addition, the mixture was heated to reflux until the evolution of gas ceased. The mixture was then distilled. In the boiling range from 142 to 145° C./10 mbar, 2150 g (95.7% of theory) of 3-cyano-2,4-dichloro-5-fluorobenzoyl chloride were obtained (content according to GC: 98.0%). fitted with metering device and gas outlet leading to a scrubber via a reflux condenser At the end of the addition the mixture was heated to reflux until the evolution of gas The mixture was then distilled

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4100 ml of thionyl chloride and 41 ml of pyridine were introduced into a stirred apparatus fitted with metering device and gas outlet leading to a scrubber via a reflux condenser, and, at 20° C., 2050 g of 3-cyano-2,4-dichloro-5-fluorobenzoic acid (99.5% strength) were introduced at the rate of hydrogen chloride/sulphur dioxide evolution. At the end of the addition, the mixture was heated to reflux until the evolution of gas ceased. The mixture was then distilled. In the boiling range from 142 to 145° C./10 mbar, 2150 g (95.7% of theory) of 3-cyano-2,4-dichloro-5-fluorobenzoyl chloride were obtained (content according to GC: 98.0%). fitted with metering device and gas outlet leading to a scrubber via a reflux condenser At the end of the addition the mixture was heated to reflux until the evolution of gas The mixture was then distilled

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Starting at room temperature, a solution of 1075 g of 2,4-dichloro-3-cyano-5-fluorobenzoyl chloride (about 94% strength, corresponding to 1010.5 g=4.00 mol) in 850 ml of dichloromethane is added dropwise to a solution of 626 g (4.372 mol) of ethyl 3-dimethylamino-acrylate and 591 g (4.572 mol) of ethyl diisopropyl-amine (Hünig's base) in 1060 ml of dichloromethane. In the course of this, the temperature rises to about 50-55° C. (dropwise addition time about 90 minutes). The reaction mixture is subsequently stirred at 50° C. for 2 hours and then employed in the next stage without further working up. Starting at room temperature rises to about 50-55° C. dropwise addition time about 90 minutes)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Starting at room temperature, a solution of 1075 g of 2,4-dichloro-3-cyano-5-fluorobenzoyl chloride (about 94% strength, corresponding to 1010.5 g=4.00 mol) in 850 ml of dichloromethane is added dropwise to a solution of 626 g (4.372 mol) of ethyl 3-dimethylamino-acrylate and 591 g (4.572 mol) of ethyl diisopropyl-amine (Hünig's base) in 1060 ml of dichloromethane. In the course of this, the temperature rises to about 50-55° C. (dropwise addition time about 90 minutes). The reaction mixture is subsequently stirred at 50° C. for 2 hours and then employed in the next stage without further working up. Starting at room temperature rises to about 50-55° C. dropwise addition time about 90 minutes)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Starting at room temperature, a solution of 1075 g of 2,4-dichloro-3-cyano-5-fluorobenzoyl chloride (about 94% strength, corresponding to 1010.5 g=4.00 mol) in 850 ml of dichloromethane is added dropwise to a solution of 626 g (4.372 mol) of ethyl 3-dimethylamino-acrylate and 591 g (4.572 mol) of ethyl diisopropyl-amine (Hünig's base) in 1060 ml of dichloromethane. In the course of this, the temperature rises to about 50-55° C. (dropwise addition time about 90 minutes). The reaction mixture is subsequently stirred at 50° C. for 2 hours and then employed in the next stage without further working up. Starting at room temperature rises to about 50-55° C. dropwise addition time about 90 minutes)