2-(2,6-difluorophenyl)acetohydrazide

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 18.6 g (142 mmol) of oxalic acid monomethylamide monoethyl ester are dissolved under a nitrogen atmosphere in 63 ml of trichloromethane, and 59 ml of a 20% solution of phosgene in toluene are added thereto. At a temperature of 5°-10°, 9.2 ml of pyridine are added dropwise. The reaction mixture is then stirred for 2 hours at 0°, nitrogen being blown through the reaction mixture during the second hour. 17.6 g (95 mmol) of 2,6-difluorophenylacetic acid hydrazide are then added. The reaction mixture is subsequently stirred for 40 minutes at room temperature, then poured onto ice-water, acidified with concentrated hydrochloric acid and extracted three times with ether. The acidic aqueous phase is rendered alkaline with concentrated ammonia solution and extracted by shaking three times with dichloromethane. The combined dichloromethane phases are washed twice with water, dried over magnesium sulphate and concentrated by evaporation. The residue is taken up in 160 ml of xylene and stirred under reflux for 9 hours. The reaction mixture is then concentrated and chromatographed over silica gel using ethyl acetate as eluant. The eluate is concentrated by evaporation and the crystalline residue is recrystallised from ethyl acetate/ether. 5-(2,6-difluorobenzyl)-4-methyl-4H-1,2,4-triazole-3-carboxylic acid ethyl ester of m.p. 127°-128° is obtained. The reaction mixture is subsequently stirred for 40 minutes at room temperature poured onto ice-water extracted three times with ether extracted by shaking three times with dichloromethane The combined dichloromethane phases are washed twice with water dried over magnesium sulphate concentrated by evaporation stirred under reflux for 9 hours The reaction mixture is then concentrated chromatographed over silica gel The eluate is concentrated by evaporation the crystalline residue is recrystallised from ethyl acetate/ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 18.6 g (142 mmol) of oxalic acid monomethylamide monoethyl ester are dissolved under a nitrogen atmosphere in 63 ml of trichloromethane, and 59 ml of a 20% solution of phosgene in toluene are added thereto. At a temperature of 5°-10°, 9.2 ml of pyridine are added dropwise. The reaction mixture is then stirred for 2 hours at 0°, nitrogen being blown through the reaction mixture during the second hour. 17.6 g (95 mmol) of 2,6-difluorophenylacetic acid hydrazide are then added. The reaction mixture is subsequently stirred for 40 minutes at room temperature, then poured onto ice-water, acidified with concentrated hydrochloric acid and extracted three times with ether. The acidic aqueous phase is rendered alkaline with concentrated ammonia solution and extracted by shaking three times with dichloromethane. The combined dichloromethane phases are washed twice with water, dried over magnesium sulphate and concentrated by evaporation. The residue is taken up in 160 ml of xylene and stirred under reflux for 9 hours. The reaction mixture is then concentrated and chromatographed over silica gel using ethyl acetate as eluant. The eluate is concentrated by evaporation and the crystalline residue is recrystallised from ethyl acetate/ether. 5-(2,6-difluorobenzyl)-4-methyl-4H-1,2,4-triazole-3-carboxylic acid ethyl ester of m.p. 127°-128° is obtained. The reaction mixture is subsequently stirred for 40 minutes at room temperature poured onto ice-water extracted three times with ether extracted by shaking three times with dichloromethane The combined dichloromethane phases are washed twice with water dried over magnesium sulphate concentrated by evaporation stirred under reflux for 9 hours The reaction mixture is then concentrated chromatographed over silica gel The eluate is concentrated by evaporation the crystalline residue is recrystallised from ethyl acetate/ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 70.4 g (0.41 mol) of 2,6-difluorophenylacetic acid, 700 ml of ethanol and 35 ml of concentrated sulphuric acid are heated under reflux for 3 hours. The reaction mixture is then concentrated by evaporation, taken up in dichloromethane and the solution is extracted by shaking in succession with water, 2N sodium carbonate solution and again with water. After drying over magnesium sulphate, the organic phase is concentrated by evaporation. The residue is dissolved in 560 ml of ethanol. After the addition of 30 ml (31 g; 0.62 mol) of hydrazine hydrate, the whole is heated under reflux for 4 days. After cooling, the resulting crystals are filtered off to yield 56.4 g (74% of the theoretical yield) of 2,6-difluorophenylacetic acid hydrazide which melts at 177°-178°. under reflux for 3 hours The reaction mixture is then concentrated by evaporation the solution is extracted After drying over magnesium sulphate the organic phase is concentrated by evaporation The residue is dissolved in 560 ml of ethanol the whole is heated under reflux for 4 days After cooling the resulting crystals are filtered off to yield 56.4 g (74% of the

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 18.6 g (142 mmol) of oxalic acid monomethylamide monoethyl ester are dissolved under a nitrogen atmosphere in 63 ml of trichloromethane, and 59 ml of a 20% solution of phosgene in toluene are added thereto. At a temperature of 5-10°, 9.2 ml of pyridine are added dropwise. The reaction mixture is then stirred for 2 hours at 0°, nitrogen being blown through the reaction mixture during the second hour. 17.6 g (95 mmol) of 2,6-difluorophenylacetic acid hydrazide are then added The reaction mixture is subsequently stirred for 40 minutes at room temperature, then poured onto ice-water, acidified with concentrated hydrochloric acid and extracted three times with ether. The acidic aqueous phase is rendered alkaline with concentrated ammonia solution and extracted by shaking three times with dichloromethane. The combined dichloromethane phases are washed twice with water, dried over magnesium sulphate and concentrated by evaporation. The residue is taken up in 160 ml of xylene and stirred under reflux for 9 hours. The reaction mixture is then concentrated and chromatographed over silica gel using ethyl acetate as eluant. The eluate is concentrated by evaporation and the crystalline residue is recrystallised from ethyl acetate/ether. 5-(2,6-difluorobenzyl)-4-methyl-4H-1,2,4-triazole-3-carboxylic acid ethyl ester of m.p. 127-128° is obtained. is subsequently stirred for 40 minutes at room temperature poured onto ice-water extracted three times with ether extracted by shaking three times with dichloromethane The combined dichloromethane phases are washed twice with water dried over magnesium sulphate concentrated by evaporation stirred under reflux for 9 hours The reaction mixture is then concentrated chromatographed over silica gel The eluate is concentrated by evaporation the crystalline residue is recrystallised from ethyl acetate/ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 18.6 g (142 mmol) of oxalic acid monomethylamide monoethyl ester are dissolved under a nitrogen atmosphere in 63 ml of trichloromethane, and 59 ml of a 20% solution of phosgene in toluene are added thereto. At a temperature of 5-10°, 9.2 ml of pyridine are added dropwise. The reaction mixture is then stirred for 2 hours at 0°, nitrogen being blown through the reaction mixture during the second hour. 17.6 g (95 mmol) of 2,6-difluorophenylacetic acid hydrazide are then added The reaction mixture is subsequently stirred for 40 minutes at room temperature, then poured onto ice-water, acidified with concentrated hydrochloric acid and extracted three times with ether. The acidic aqueous phase is rendered alkaline with concentrated ammonia solution and extracted by shaking three times with dichloromethane. The combined dichloromethane phases are washed twice with water, dried over magnesium sulphate and concentrated by evaporation. The residue is taken up in 160 ml of xylene and stirred under reflux for 9 hours. The reaction mixture is then concentrated and chromatographed over silica gel using ethyl acetate as eluant. The eluate is concentrated by evaporation and the crystalline residue is recrystallised from ethyl acetate/ether. 5-(2,6-difluorobenzyl)-4-methyl-4H-1,2,4-triazole-3-carboxylic acid ethyl ester of m.p. 127-128° is obtained. is subsequently stirred for 40 minutes at room temperature poured onto ice-water extracted three times with ether extracted by shaking three times with dichloromethane The combined dichloromethane phases are washed twice with water dried over magnesium sulphate concentrated by evaporation stirred under reflux for 9 hours The reaction mixture is then concentrated chromatographed over silica gel The eluate is concentrated by evaporation the crystalline residue is recrystallised from ethyl acetate/ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 70.4 g (0.41 mol) of 2,6-difluorophenylacetic acid, 700 ml of ethanol and 35 ml of concentrated sulphuric acid are heated under reflux for 3 hours. The reaction mixture is then concentrated by evaporation, taken up in dichloromethane and the solution is extracted by shaking in succession with water, 2N sodium carbonate solution and again with water. After drying over magnesium sulphate, the organic phase is concentrated by evaporation. The residue is dissolved in 560 ml of ethanol. After the addition of 30 ml (31 g; 0.62 mol) of hydrazine hydrate, the whole is heated under reflux for 4 days. After cooling, the resulting crystals are filtered off to yield 56.4 g (74% of the theoretical yield) of 2,6-difluorophenylacetic acid hydrazide which melts at 177-178°. under reflux for 3 hours The reaction mixture is then concentrated by evaporation the solution is extracted After drying over magnesium sulphate the organic phase is concentrated by evaporation The residue is dissolved in 560 ml of ethanol the whole is heated under reflux for 4 days After cooling the resulting crystals are filtered off to yield 56.4 g (74% of the

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 70.4 g (0.41 mol) of 2,6-difluorophenylacetic acid, 700 ml of ethanol and 35 ml of concentrated sulphuric acid are heated under reflux for 3 hours. The reaction mixture is then concentrated by evaporation, taken up in dichloromethane and the solution is extracted by shaking in succession with water, 2N sodium carbonate solution and again with water. After drying over magnesium sulphate, the organic phase is concentrated by evaporation. The residue is dissolved in 560 ml of ethanol. After the addition of 30 ml (31 g; 0.62 mol) of hydrazine hydrate, the whole is heated under reflux for 4 days. After cooling, the resulting crystals are filtered off to yield 56.4 g (74% of the theoretical yield) of 2,6-difluorophenylacetic acid hydrazide which melts at 177-178°. under reflux for 3 hours The reaction mixture is then concentrated by evaporation the solution is extracted After drying over magnesium sulphate the organic phase is concentrated by evaporation The residue is dissolved in 560 ml of ethanol the whole is heated under reflux for 4 days After cooling the resulting crystals are filtered off to yield 56.4 g (74% of the

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 18.6 g (142 mmol) of oxalic acid monomethylamide monoethyl ester are dissolved under a nitrogen atmosphere in 63 ml of trichloromethane, and 59 ml of a 20% solution of phosgene in toluene are added thereto. At a temperature of 5°-10°, 9.2 ml of pyridine are added dropwise. The reaction mixture is then stirred for 2 hours at 0°, nitrogen being blown through the reaction mixture during the second hour. 17.6 g (95 mmol) of 2,6-difluorophenylacetic acid hydrazide are then added. The reaction mixture is subsequently stirred for 40 minutes at room temperature, then poured onto ice-water, acidified with concentrated hydrochloric acid and extracted three times with ether. The acidic aqueous phase is rendered alkaline with concentrated ammonia solution and extracted by shaking three times with dichloromethane. The combined dichloromethane phases are washed twice with water, dried over magnesium sulphate and concentrated by evaporation. The residue is taken up in 160 ml of xylene and stirred under reflux for 9 hours. The reaction mixture is then concentrated and chromatographed over silica gel using ethyl acetate as eluant. The eluate is concentrated by evaporation and the crystalline residue is recrystallised from ethyl acetate/ether. 5-(2,6-difluorobenzyl)-4-methyl-4H-1,2,4-triazole-3-carboxylic acid ethyl ester of m.p. 127°-128° is obtained. The reaction mixture is subsequently stirred for 40 minutes at room temperature poured onto ice-water extracted three times with ether extracted by shaking three times with dichloromethane The combined dichloromethane phases are washed twice with water dried over magnesium sulphate concentrated by evaporation stirred under reflux for 9 hours The reaction mixture is then concentrated chromatographed over silica gel The eluate is concentrated by evaporation the crystalline residue is recrystallised from ethyl acetate/ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 70.4 g (0.41 mol) of 2,6-difluorophenylacetic acid, 700 ml of ethanol and 35 ml of concentrated sulphuric acid are heated under reflux for 3 hours. The reaction mixture is then concentrated by evaporation, taken up in dichloromethane and the solution is extracted by shaking in succession with water, 2N sodium carbonate solution and again with water. After drying over magnesium sulphate, the organic phase is concentrated by evaporation. The residue is dissolved in 560 ml of ethanol. After the addition of 30 ml (31 g; 0.62 mol) of hydrazine hydrate, the whole is heated under reflux for 4 days. After cooling, the resulting crystals are filtered off to yield 56.4 g (74% of the theoretical yield) of 2,6-difluorophenylacetic acid hydrazide which melts at 177°-178°. under reflux for 3 hours The reaction mixture is then concentrated by evaporation the solution is extracted After drying over magnesium sulphate the organic phase is concentrated by evaporation The residue is dissolved in 560 ml of ethanol the whole is heated under reflux for 4 days After cooling the resulting crystals are filtered off to yield 56.4 g (74% of the