ethyl 2,2-dichloroacetate

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

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 100 mL of 1M BH3-THF complex (100 mmol) were added to 170 mL of dry THF under a blanket of nitrogen at room temperature. 12.3 mL of cis-1,5-cyclooctadiene (100 mmol) were added dropwise to this mixture within a period of 5 minutes, and the temperature rose to 45° C. The reaction mixture was heated under reflux over a period of 1.5 h, again cooled to 45° C., and 10.1 mL of cyclohexene (100 mmol) were added and stirring was continued for a further 2 h at 45° C. After the reaction mixture had been cooled in an ice bath, 12.2 mL of ethyldichloroacetate (100 mmol) in 50 mL of tert-butanol were added, stirring was continued for a further 15 minutes and 1M potassium tert-butylate (100 mmol, 100 mL) was added dropwise within a further 15 minutes. The reaction mixture was then stirred over a period of 15 minutes, 33 mL of 3M sodium acetate solution (100 mmol) were added and 22.5 mL of 30% strength aq. H2O2 solution (750 mmol) were added dropwise. The mixture was stirred at room temperature over a period of 30 minutes, then salted out with NaCl, the organic phase dried over MgSO4 and the solvent removed under reduced pressure. Following washing of the residual solid matter with tert-butylmethyl ether, cyclohexane/tert-butylmethyl ether (9:1), tert-butylmethyl ether, and EA, there were obtained 7.6 g (37.4%) of product. rose to 45° C The reaction mixture was heated under reflux over a period of 1.5 h After the reaction mixture had been cooled in an ice bath stirring was continued for a further 15 minutes The reaction mixture was then stirred over a period of 15 minutes The mixture was stirred at room temperature over a period of 30 minutes the organic phase dried over MgSO4 the solvent removed under reduced pressure Following washing of the residual solid matter with tert-butylmethyl ether, cyclohexane/tert-butylmethyl ether (9:1), tert-butylmethyl ether, and EA

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 100 mL of 1M BH3-THF complex (100 mmol) were added to 170 mL of dry THF under a blanket of nitrogen at room temperature. 12.3 mL of cis-1,5-cyclooctadiene (100 mmol) were added dropwise to this mixture within a period of 5 minutes, and the temperature rose to 45° C. The reaction mixture was heated under reflux over a period of 1.5 h, again cooled to 45° C., and 10.1 mL of cyclohexene (100 mmol) were added and stirring was continued for a further 2 h at 45° C. After the reaction mixture had been cooled in an ice bath, 12.2 mL of ethyldichloroacetate (100 mmol) in 50 mL of tert-butanol were added, stirring was continued for a further 15 minutes and 1M potassium tert-butylate (100 mmol, 100 mL) was added dropwise within a further 15 minutes. The reaction mixture was then stirred over a period of 15 minutes, 33 mL of 3M sodium acetate solution (100 mmol) were added and 22.5 mL of 30% strength aq. H2O2 solution (750 mmol) were added dropwise. The mixture was stirred at room temperature over a period of 30 minutes, then salted out with NaCl, the organic phase dried over MgSO4 and the solvent removed under reduced pressure. Following washing of the residual solid matter with tert-butylmethyl ether, cyclohexane/tert-butylmethyl ether (9:1), tert-butylmethyl ether, and EA, there were obtained 7.6 g (37.4%) of product. rose to 45° C The reaction mixture was heated under reflux over a period of 1.5 h After the reaction mixture had been cooled in an ice bath stirring was continued for a further 15 minutes The reaction mixture was then stirred over a period of 15 minutes The mixture was stirred at room temperature over a period of 30 minutes the organic phase dried over MgSO4 the solvent removed under reduced pressure Following washing of the residual solid matter with tert-butylmethyl ether, cyclohexane/tert-butylmethyl ether (9:1), tert-butylmethyl ether, and EA

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

Procedure: In a manner analogous to that described in Example 4, 21.3 g (64 mmol) of 4-(2,5-dichlorophenylsulphonyl)-5-methyl-1,2-benzenediol, 10.0 g (64 mmol) of dichloroacetic acid ethyl ester and 44.2 g (320 mmol) of potassium carbonate in 160 ml of 1,2-dimethoxyethane are boiled under reflux. After 18 hours, the reaction mixture is filtered and the solid filtration residue is washed twice with 1,2-dimethoxyethane. 44 g of fresh potassium carbonate and 10 g of dichloroacetic acid ethyl ester are added to the combined organic solutions and the whole is stirred for 5 minutes using a high-speed stirrer and boiled, while stirring normally, for a further 17 hours. Working up is carried out in a manner analogous to that described in Example 10. After drying carefully, 5-(2,5-dichlorophenylsulphonyl)-6-methyl-1,3-benzodioxole-2-carboxylic acid is obtained in the form of white crystals having a melting point of 155°-157° (from diisopropyl ether). under reflux the reaction mixture is filtered the solid filtration residue is washed twice with 1,2-dimethoxyethane 44 g of fresh potassium carbonate and 10 g of dichloroacetic acid ethyl ester are added to the combined organic solutions while stirring normally, for a further 17 hours After drying carefully

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

Procedure: In a manner analogous to that described in Example 4, 21.3 g (64 mmol) of 4-(2,5-dichlorophenylsulphonyl)-5-methyl-1,2-benzenediol, 10.0 g (64 mmol) of dichloroacetic acid ethyl ester and 44.2 g (320 mmol) of potassium carbonate in 160 ml of 1,2-dimethoxyethane are boiled under reflux. After 18 hours, the reaction mixture is filtered and the solid filtration residue is washed twice with 1,2-dimethoxyethane. 44 g of fresh potassium carbonate and 10 g of dichloroacetic acid ethyl ester are added to the combined organic solutions and the whole is stirred for 5 minutes using a high-speed stirrer and boiled, while stirring normally, for a further 17 hours. Working up is carried out in a manner analogous to that described in Example 10. After drying carefully, 5-(2,5-dichlorophenylsulphonyl)-6-methyl-1,3-benzodioxole-2-carboxylic acid is obtained in the form of white crystals having a melting point of 155°-157° (from diisopropyl ether). under reflux the reaction mixture is filtered the solid filtration residue is washed twice with 1,2-dimethoxyethane 44 g of fresh potassium carbonate and 10 g of dichloroacetic acid ethyl ester are added to the combined organic solutions while stirring normally, for a further 17 hours After drying carefully

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

Procedure: In a manner analogous to that described in Example 4, 30.0 g (111 mmol) of 4-methyl-5-(2-thienylsulphonyl)-1,2-benzenediol, 17.4 g (111 mmol) of dichloroacetic acid ethyl ester and 76.7 g (555 mmol) of potassium carbonate in 300 ml of 1,2-dimethoxyethane are boiled under reflux. After 18 hours, the reaction mixture is poured into water, stirred for one hour at room temperature and then adjusted to pH 1-2 by means of hydrochloric acid. Some of the 1,2-dimethoxyethane is distilled off in vacuo and the mixture remaining is extracted with ethyl acetate. The combined organic phases are washed with water and saturated sodium chloride solution, dried over sodium sulphate and concentrated by evaporation in a rotary evaporator. The resulting dark-red oil is chromatographed over silica gel. As eluant, a mixture of chloroform/methanol/concentrated ammonia in a ratio of 40:10:1 is used until elution of the starting diol, then an analogous mixture in a ratio of 12:5:1 is used. The uniform fractions are combined and concentrated almost completely by evaporation. Ice/water is added to the residue and the pH is adjusted to 1-2 with concentrated hydrochloric acid. The acidic solution is extracted with ethyl acetate. The combined organic phases are washed, dried and concentrated by evaporation. The residue is boiled in diisopropyl ether and the black sludge formed is removed by decanting. The clear solution is concentrated to a large extent and the substance which has crystallised out is filtered off with suction. The crystals are recrystallised from 1,2-dichloroethane, yielding 5-methyl-6-(2-thienylsulphonyl)-1,3-benzodioxole-2-carboxylic acid in the form of white crystals having a melting point of 162.5°-164.5°. under reflux Some of the 1,2-dimethoxyethane is distilled off in vacuo the mixture remaining is extracted with ethyl acetate The combined organic phases are washed with water and saturated sodium chloride solution dried over sodium sulphate concentrated by evaporation in a rotary evaporator The resulting dark-red oil is chromatographed over silica gel As eluant, a mixture of chloroform/methanol/concentrated ammonia in a ratio of 40:10:1 is used until elution of the starting diol concentrated almost completely by evaporation Ice/water is added to the residue The acidic solution is extracted with ethyl acetate The combined organic phases are washed dried concentrated by evaporation the black sludge formed is removed by decanting The clear solution is concentrated to a large extent the substance which has crystallised out is filtered off with suction The crystals are recrystallised from 1,2-dichloroethane

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

Procedure: A suspension of 72.8 g (526 mmol) of freshly calcined potassium carbonate in 300 ml of 1,2-dimethoxyethane is stirred under nitrogen for 10 minutes using a high-speed stirrer and then, while stirring normally, 37.0 g (105.3 mmol) of 4-(3-acetamido-4-methoxyphenylsulphonyl)-5-methyl-1,2-benzenediol, 16.5 g (105.3 mmol) of dichloroacetic acid ethyl ester and 3 g of tetrabutylammonium bromide are added. The mixture is boiled under reflux, 300 ml of acetone are added, the whole is boiled under reflux for 3 more hours, a further 60 g of potassium carbonate and 16.5 g of dichloroacetic acid ethyl ester are added, and the whole is boiled under reflux for 9 more hours. The reaction mixture is poured into water and acidified to pH 1-2 with hydrochloric acid. Some of the solvent is evaporated off in vacuo and the aqueous phase remaining is extracted with ethyl acetate. The combined organic phases are washed with water and saturated sodium chloride solution, dried over sodium sulphate and concentrated by evaporation in a rotary evaporator. The residue is recrystallised four times from acetonitrile, yielding 5-(3-acetamido-4-methoxyphenylsulphonyl)-6-methyl-1,3-benzodioxole-2-carboxylic acid in the form of white crystals having a melting point of 230° (sintering at 150°). while stirring normally under reflux under reflux for 3 more hours under reflux for 9 more hours Some of the solvent is evaporated off in vacuo the aqueous phase remaining is extracted with ethyl acetate The combined organic phases are washed with water and saturated sodium chloride solution dried over sodium sulphate concentrated by evaporation in a rotary evaporator The residue is recrystallised four times from acetonitrile

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

Procedure: A suspension of 72.8 g (526 mmol) of freshly calcined potassium carbonate in 300 ml of 1,2-dimethoxyethane is stirred under nitrogen for 10 minutes using a high-speed stirrer and then, while stirring normally, 37.0 g (105.3 mmol) of 4-(3-acetamido-4-methoxyphenylsulphonyl)-5-methyl-1,2-benzenediol, 16.5 g (105.3 mmol) of dichloroacetic acid ethyl ester and 3 g of tetrabutylammonium bromide are added. The mixture is boiled under reflux, 300 ml of acetone are added, the whole is boiled under reflux for 3 more hours, a further 60 g of potassium carbonate and 16.5 g of dichloroacetic acid ethyl ester are added, and the whole is boiled under reflux for 9 more hours. The reaction mixture is poured into water and acidified to pH 1-2 with hydrochloric acid. Some of the solvent is evaporated off in vacuo and the aqueous phase remaining is extracted with ethyl acetate. The combined organic phases are washed with water and saturated sodium chloride solution, dried over sodium sulphate and concentrated by evaporation in a rotary evaporator. The residue is recrystallised four times from acetonitrile, yielding 5-(3-acetamido-4-methoxyphenylsulphonyl)-6-methyl-1,3-benzodioxole-2-carboxylic acid in the form of white crystals having a melting point of 230° (sintering at 150°). while stirring normally under reflux under reflux for 3 more hours under reflux for 9 more hours Some of the solvent is evaporated off in vacuo the aqueous phase remaining is extracted with ethyl acetate The combined organic phases are washed with water and saturated sodium chloride solution dried over sodium sulphate concentrated by evaporation in a rotary evaporator The residue is recrystallised four times from acetonitrile

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

Procedure: In a manner analogous to that described in Example 4, using 25.0 g (83.7 mmol) of 4-(4-chlorophenylsulphonyl)-5-methyl-1,2-benzenediol, 13.2 g (83.7 mmol) of dichloroacetic acid ethyl ester, 57 g (418 mmol) of potassium carbonate and 220 ml of 1,2-dimethoxyethane, with subsequent hydrolysis with sodium hydroxide solution in methanol, the desired 5-(4-chlorophenylsulphonyl)-6-methyl-1,3-benzodioxole-2-carboxylic acid is obtained in the form of white crystals having a melting point of 169°-171° (from 1,2-dichloroethane).

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

Procedure: A suspension of 12.0 g (43.1 mmol) of 4-methyl-5-(4-methylphenylsulphonyl)-1,2-benzenediol and 30 g (216 mmol) of freshly calcined potassium carbonate in 200 ml of dry 1,2-dimethoxyethane is stirred for 5 minutes, under nitrogen, using a high-speed stirrer. In the course of this the temperature rises to 75°. Then, while stirring moderately (propeller stirrer), there is added dropwise thereto, in the course of one hour, a solution of 6.77 g (43.1 mmol) of dichloroacetic acid ethyl ester in 50 ml of dry 1,2-dimethoxyethane and the mixture is then boiled under reflux for 15 hours. It is subsequently poured onto an ice/water mixture and adjusted to pH 1-2 with concentrated hydrochloric acid. Some of the 1,2-dimethoxyethane is evaporated off in a rotary evaporator and the solution remaining is extracted with ethyl acetate. The combined organic phases are washed with water and saturated sodium chloride solution, dried over sodium sulphate and concentrated by evaporation in a rotary evaporator. The resulting black oil is dissolved in ethanol, 0.5 g of p-toluenesulphonic acid is added, and the whole is boiled under reflux in a vessel provided with a Soxhlet attachment that is filled with molecular sieve. The ethanolic solution is then concentrated completely by evaporation and chromatographed over silica gel (solvent ethyl acetate/hexane in a ratio of 1:1). The uniform fractions containing the desired substance are combined and concentrated by evaporation. In this manner 5-methyl-6-(4-methylphenylsulphonyl)-1,3-benzodioxole-2-carboxylic acid ethyl ester is obtained in the form of a yellow oil, which can be hydrolysed directly. rises to 75° Then, while stirring moderately (propeller stirrer), there is added dropwise in the course of one hour under reflux for 15 hours Some of the 1,2-dimethoxyethane is evaporated off in a rotary evaporator the solution remaining is extracted with ethyl acetate The combined organic phases are washed with water and saturated sodium chloride solution dried over sodium sulphate concentrated by evaporation in a rotary evaporator The resulting black oil is dissolved in ethanol 0.5 g of p-toluenesulphonic acid is added under reflux in a vessel provided with a Soxhlet attachment that is filled with molecular sieve The ethanolic solution is then concentrated completely by evaporation chromatographed over silica gel (solvent ethyl acetate/hexane in a ratio of 1:1) The uniform fractions containing the desired substance concentrated by evaporation

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

Procedure: 27.7 g (200 mmol) of anhydrous potassium carbonate are added to a suspension of 10.6 g (40 mmol) of 4-methyl-5-phenylsulphonyl-1,2-benzenediol in 65 ml of cold 1,2-dimethoxyethane. While stirring vigorously, a solution of 7.85 g (50 mmol) of dichloroacetic acid ethyl ester in 5 ml of 1,2-dimethoxyethane is added dropwise thereto in the course of 30 minutes. The mixture is stirred for a further hour at room temperature and is then boiled under reflux for 3 hours while stirring. It is then cooled to 30°, water is added, and the whole is stirred for 30 minutes and adjusted to pH 1-2 with hydrochloric acid. Some of the 1,2-dimethoxyethane is removed in a rotary evaporator and the solution remaining is extracted three times with ethyl acetate. The combined ethyl acetate solutions are washed with water, and then with saturated sodium chloride solution, dried over sodium sulphate, treated with activated carbon and concentrated by evaporation. The resulting yellow-green oil is crystallised from ethyl acetate/hexane. The sand-coloured crystals are dissolved in ethyl acetate and treated again with activated carbon. The solvent is removed in a rotary evaporator. The yellow oil remaining is crystallised from methylene chloride at 0°, yielding 5-methyl-6-phenylsulphonyl-1,3-benzodioxole-2-carboxylic acid having a melting point of 169°-171°. in the course of 30 minutes The mixture is stirred for a further hour at room temperature under reflux for 3 hours while stirring It is then cooled to 30° the whole is stirred for 30 minutes Some of the 1,2-dimethoxyethane is removed in a rotary evaporator the solution remaining is extracted three times with ethyl acetate The combined ethyl acetate solutions are washed with water with saturated sodium chloride solution, dried over sodium sulphate treated with activated carbon concentrated by evaporation The resulting yellow-green oil is crystallised from ethyl acetate/hexane The sand-coloured crystals are dissolved in ethyl acetate treated again with activated carbon The solvent is removed in a rotary evaporator The yellow oil remaining is crystallised from methylene chloride at 0°

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

Procedure: 27.7 g (200 mmol) of anhydrous potassium carbonate are added to a suspension of 10.6 g (40 mmol) of 4-methyl-5-phenylsulphonyl-1,2-benzenediol in 65 ml of cold 1,2-dimethoxyethane. While stirring vigorously, a solution of 7.85 g (50 mmol) of dichloroacetic acid ethyl ester in 5 ml of 1,2-dimethoxyethane is added dropwise thereto in the course of 30 minutes. The mixture is stirred for a further hour at room temperature and is then boiled under reflux for 3 hours while stirring. It is then cooled to 30°, water is added, and the whole is stirred for 30 minutes and adjusted to pH 1-2 with hydrochloric acid. Some of the 1,2-dimethoxyethane is removed in a rotary evaporator and the solution remaining is extracted three times with ethyl acetate. The combined ethyl acetate solutions are washed with water, and then with saturated sodium chloride solution, dried over sodium sulphate, treated with activated carbon and concentrated by evaporation. The resulting yellow-green oil is crystallised from ethyl acetate/hexane. The sand-coloured crystals are dissolved in ethyl acetate and treated again with activated carbon. The solvent is removed in a rotary evaporator. The yellow oil remaining is crystallised from methylene chloride at 0°, yielding 5-methyl-6-phenylsulphonyl-1,3-benzodioxole-2-carboxylic acid having a melting point of 169°-171°. in the course of 30 minutes The mixture is stirred for a further hour at room temperature under reflux for 3 hours while stirring It is then cooled to 30° the whole is stirred for 30 minutes Some of the 1,2-dimethoxyethane is removed in a rotary evaporator the solution remaining is extracted three times with ethyl acetate The combined ethyl acetate solutions are washed with water with saturated sodium chloride solution, dried over sodium sulphate treated with activated carbon concentrated by evaporation The resulting yellow-green oil is crystallised from ethyl acetate/hexane The sand-coloured crystals are dissolved in ethyl acetate treated again with activated carbon The solvent is removed in a rotary evaporator The yellow oil remaining is crystallised from methylene chloride at 0°