1-Chloromethoxy-2,4-dichlorobenzene

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: To a solution of mercapto-acetic acid ethyl ester (2.4 g, 19.86 mmol) in dry DMF (20 mL) was added NaH (556 mg, 23.27 mmol, 60% in mineral oil). The mixture was stirred for 30 min. at room temperature followed by dropwise addition of 2,4-dichloro-1-chloromethoxy-benzene (3.5 g, 16.55 mmol), stirring was continued for 16 hrs at ambient temperature. The reaction was quenched by addition of water (50 mL) and extracted with diethyl ether (2×50 mL). The combined organic phases were washed with saturated aq. ammonium chloride (50 mL), dried (Na2SO4), filtered and evaporated in vacuo. The residue was dissolved in EtOH (20 mL) and to this solution was added aq. 32% NaOH (1 mL) and water (10 mL). Stirring was continued for 16 hrs at room temperature. The volatiles were evaporated in vacuo, water (20 mL) was added followed by washing with diethyl ether (20 mL). The aqueous phase was acidified to pH˜1 with conc. HCl followed by extraction with diethyl ether (2×25 mL). The combined organic phases were dried (Na2SO4), filtered and the solvent evaporated in vacuo affording 2.5 g (57%) of crude (2,4-dichloro-phenoxymethylsulfanyl)-acetic acid as a solid. stirring was continued for 16 hrs at ambient temperature The reaction was quenched by addition of water (50 mL) extracted with diethyl ether (2×50 mL) The combined organic phases were washed with saturated aq. ammonium chloride (50 mL) dried (Na2SO4) filtered evaporated in vacuo The residue was dissolved in EtOH (20 mL) and to this solution was added aq. 32% NaOH (1 mL) and water (10 mL) Stirring was continued for 16 hrs at room temperature The volatiles were evaporated in vacuo, water (20 mL) was added by washing with diethyl ether (20 mL) followed by extraction with diethyl ether (2×25 mL) The combined organic phases were dried (Na2SO4) filtered the solvent evaporated in vacuo

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

実験手順: To an ice-water cooled solution of 2,4-dichloro-1-methanesulfinylmethoxy-benzene (8 g, 33.46 mmol) in DCM (100 mL) was added dropwise a solution of acetylchloride (2.6 mL, 36.80 mmol) in DCM (10 mL). The reaction mixture was allowed to reach room temperature during 2 hrs at which time the volatiles were evaporated in vacuo affording ˜7 g of crude 2,4-dichloro-1-chloromethoxy-benzene which was used without further purification. the volatiles were evaporated in vacuo

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

実験手順: A solution of 28 g (0.25 mol) of potassium tert.-butylate in 120 ml of tetrahydrofuran was slowly added dropwise to a solution of 33.6 g (0.2 mol) of methyl 2-mercapto-benzoate in 50 ml of tetrahydrofuran at 5° C. At the end of the dropwise addition, stirring was continued at 5° C. for a further 30 minutes. The solid product precipitated was filtered off with suction and dissolved in 100 ml of dimethylformamide. A solution of 42.3 g (0.2 mol) of chloromethyl 2,4-dichlorophenyl ether in 60 ml of dimethylformamide was added dropwise to this solution, while stirring at 25° C. The mixture was subsequently stirred at 30° C. for 1 hour and then worked up by stirring into 1.5 liters of ice-water. The suspension thereby formed was filtered off with suction and the solid product precipitated was dried in air. 62 g (90.4% of theory) of 1-(2,4-dichlorophenoxy)-1 -(2-methoxycarbonyl-phenylthio)-methane were obtained in this manner in the form of colourless crystals of melting point 122°-124° C. At the end of the dropwise addition The solid product precipitated was filtered off with suction dissolved in 100 ml of dimethylformamide while stirring at 25° C The mixture was subsequently stirred at 30° C. for 1 hour The suspension thereby formed was filtered off with suction the solid product precipitated was dried in air

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

実験手順: A solution of 28 g (0.25 mol) of potassium tert.-butylate in 120 ml of tetrahydrofuran was slowly added dropwise to a solution of 33.6 g (0.2 mol) of methyl 2-mercapto-benzoate in 50 ml of tetrahydrofuran at 5° C. At the end of the dropwise addition, stirring was continued at 5° C. for a further 30 minutes. The solid product precipitated was filtered off with suction and dissolved in 100 ml of dimethylformamide. A solution of 42.3 g (0.2 mol) of chloromethyl 2,4-dichlorophenyl ether in 60 ml of dimethylformamide was added dropwise to this solution, while stirring at 25° C. The mixture was subsequently stirred at 30° C. for 1 hour and then worked up by stirring into 1.5 liters of ice-water. The suspension thereby formed was filtered off with suction and the solid product precipitated was dried in air. 62 g (90.4% of theory) of 1-(2,4-dichlorophenoxy)-1 -(2-methoxycarbonyl-phenylthio)-methane were obtained in this manner in the form of colourless crystals of melting point 122°-124° C. At the end of the dropwise addition The solid product precipitated was filtered off with suction dissolved in 100 ml of dimethylformamide while stirring at 25° C The mixture was subsequently stirred at 30° C. for 1 hour The suspension thereby formed was filtered off with suction the solid product precipitated was dried in air

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared in a manner similar to that described in Example 6 by the addition of a solution of 1-chloromethoxy-2,4-dichlorobenzene (see preparation 6) (5 mmol) in dichloromethane (25 ml) to a solution of 5-chloropyrimidin-2-one (5 mmol) and triethylamine (5 mmol) in dichloromethane (75 ml). The mixture was stirred at room temperature for 2 h and at 40° C. for 7 h before being worked up as above; yield 1.30 g (80%), isomer ratio 3:1. The title compound crystallized from DMSO: m.p. 170° C. 1H NMR (TFA): δ 6.10 (CH2), 6.9-7.4 (Ph), 9.0-9.2 (H-4, H-6). IR (KBr): 1680 cm-1 (CO). MS (70 eV, m/z (% rel. int.)) 304 (l,M), 162 (3), 145 (35), 143 (100), 116 (28). The title compound crystallized from DMSO

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared in a manner similar to that described in Example 6 by the addition of a solution of 1-chloromethoxy-2,4-dichlorobenzene (see preparation 6) (5 mmol) in dichloromethane (25 ml) to a solution of 5-chloropyrimidin-2-one (5 mmol) and triethylamine (5 mmol) in dichloromethane (75 ml). The mixture was stirred at room temperature for 2 h and at 40° C. for 7 h before being worked up as above; yield 1.30 g (80%), isomer ratio 3:1. The title compound crystallized from DMSO: m.p. 170° C. 1H NMR (TFA): δ 6.10 (CH2), 6.9-7.4 (Ph), 9.0-9.2 (H-4, H-6). IR (KBr): 1680 cm-1 (CO). MS (70 eV, m/z (% rel. int.)) 304 (l,M), 162 (3), 145 (35), 143 (100), 116 (28). The title compound crystallized from DMSO

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

実験手順: To a solution of mercapto-acetic acid ethyl ester (2.4 g, 19.86 mmol) in dry DMF (20 mL) was added NaH (556 mg, 23.27 mmol, 60% in mineral oil). The mixture was stirred for 30 min. at room temperature followed by dropwise addition of 2,4-dichloro-1-chloromethoxy-benzene (3.5 g, 16.55 mmol), stirring was continued for 16 hrs at ambient temperature. The reaction was quenched by addition of water (50 mL) and extracted with diethyl ether (2×50 mL). The combined organic phases were washed with saturated aq. ammonium chloride (50 mL), dried (Na2SO4), filtered and evaporated in vacuo. The residue was dissolved in EtOH (20 mL) and to this solution was added aq. 32% NaOH (1 mL) and water (10 mL). Stirring was continued for 16 hrs at room temperature. The volatiles were evaporated in vacuo, water (20 mL) was added followed by washing with diethyl ether (20 mL). The aqueous phase was acidified to pH˜1 with conc. HCl followed by extraction with diethyl ether (2×25 mL). The combined organic phases were dried (Na2SO4), filtered and the solvent evaporated in vacuo affording 2.5 g (57%) of crude (2,4-dichloro-phenoxymethylsulfanyl)-acetic acid as a solid. stirring was continued for 16 hrs at ambient temperature The reaction was quenched by addition of water (50 mL) extracted with diethyl ether (2×50 mL) The combined organic phases were washed with saturated aq. ammonium chloride (50 mL) dried (Na2SO4) filtered evaporated in vacuo The residue was dissolved in EtOH (20 mL) and to this solution was added aq. 32% NaOH (1 mL) and water (10 mL) Stirring was continued for 16 hrs at room temperature The volatiles were evaporated in vacuo, water (20 mL) was added by washing with diethyl ether (20 mL) followed by extraction with diethyl ether (2×25 mL) The combined organic phases were dried (Na2SO4) filtered the solvent evaporated in vacuo

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

実験手順: To a solution of mercapto-acetic acid ethyl ester (2.4 g, 19.86 mmol) in dry DMF (20 mL) was added NaH (556 mg, 23.27 mmol, 60% in mineral oil). The mixture was stirred for 30 min. at room temperature followed by dropwise addition of 2,4-dichloro-1-chloromethoxy-benzene (3.5 g, 16.55 mmol), stirring was continued for 16 hrs at ambient temperature. The reaction was quenched by addition of water (50 mL) and extracted with diethyl ether (2×50 mL). The combined organic phases were washed with saturated aq. ammonium chloride (50 mL), dried (Na2SO4), filtered and evaporated in vacuo. The residue was dissolved in EtOH (20 mL) and to this solution was added aq. 32% NaOH (1 mL) and water (10 mL). Stirring was continued for 16 hrs at room temperature. The volatiles were evaporated in vacuo, water (20 mL) was added followed by washing with diethyl ether (20 mL). The aqueous phase was acidified to pH˜1 with conc. HCl followed by extraction with diethyl ether (2×25 mL). The combined organic phases were dried (Na2SO4), filtered and the solvent evaporated in vacuo affording 2.5 g (57%) of crude (2,4-dichloro-phenoxymethylsulfanyl)-acetic acid as a solid. stirring was continued for 16 hrs at ambient temperature The reaction was quenched by addition of water (50 mL) extracted with diethyl ether (2×50 mL) The combined organic phases were washed with saturated aq. ammonium chloride (50 mL) dried (Na2SO4) filtered evaporated in vacuo The residue was dissolved in EtOH (20 mL) and to this solution was added aq. 32% NaOH (1 mL) and water (10 mL) Stirring was continued for 16 hrs at room temperature The volatiles were evaporated in vacuo, water (20 mL) was added by washing with diethyl ether (20 mL) followed by extraction with diethyl ether (2×25 mL) The combined organic phases were dried (Na2SO4) filtered the solvent evaporated in vacuo

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

実験手順: To an ice-water cooled solution of 2,4-dichloro-1-methanesulfinylmethoxy-benzene (8 g, 33.46 mmol) in DCM (100 mL) was added dropwise a solution of acetylchloride (2.6 mL, 36.80 mmol) in DCM (10 mL). The reaction mixture was allowed to reach room temperature during 2 hrs at which time the volatiles were evaporated in vacuo affording ˜7 g of crude 2,4-dichloro-1-chloromethoxy-benzene which was used without further purification. the volatiles were evaporated in vacuo

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

実験手順: A solution of 28 g (0.25 mol) of potassium tert.-butylate in 120 ml of tetrahydrofuran was slowly added dropwise to a solution of 33.6 g (0.2 mol) of methyl 2-mercapto-benzoate in 50 ml of tetrahydrofuran at 5° C. At the end of the dropwise addition, stirring was continued at 5° C. for a further 30 minutes. The solid product precipitated was filtered off with suction and dissolved in 100 ml of dimethylformamide. A solution of 42.3 g (0.2 mol) of chloromethyl 2,4-dichlorophenyl ether in 60 ml of dimethylformamide was added dropwise to this solution, while stirring at 25° C. The mixture was subsequently stirred at 30° C. for 1 hour and then worked up by stirring into 1.5 liters of ice-water. The suspension thereby formed was filtered off with suction and the solid product precipitated was dried in air. 62 g (90.4% of theory) of 1-(2,4-dichlorophenoxy)-1 -(2-methoxycarbonyl-phenylthio)-methane were obtained in this manner in the form of colourless crystals of melting point 122°-124° C. At the end of the dropwise addition The solid product precipitated was filtered off with suction dissolved in 100 ml of dimethylformamide while stirring at 25° C The mixture was subsequently stirred at 30° C. for 1 hour The suspension thereby formed was filtered off with suction the solid product precipitated was dried in air

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared in a manner similar to that described in Example 6 by the addition of a solution of 1-chloromethoxy-2,4-dichlorobenzene (see preparation 6) (5 mmol) in dichloromethane (25 ml) to a solution of 5-chloropyrimidin-2-one (5 mmol) and triethylamine (5 mmol) in dichloromethane (75 ml). The mixture was stirred at room temperature for 2 h and at 40° C. for 7 h before being worked up as above; yield 1.30 g (80%), isomer ratio 3:1. The title compound crystallized from DMSO: m.p. 170° C. 1H NMR (TFA): δ 6.10 (CH2), 6.9-7.4 (Ph), 9.0-9.2 (H-4, H-6). IR (KBr): 1680 cm-1 (CO). MS (70 eV, m/z (% rel. int.)) 304 (l,M), 162 (3), 145 (35), 143 (100), 116 (28). The title compound crystallized from DMSO