methyl 2-hydroxy-3-methoxybenzoate

反応条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3.4 g (0.024 mol) of chlorosulfonyl isocyanate are added dropwise to a solution of 3.6 g (0.02 mol) of methyl 3-methoxy-salicylate in 20 ml of xylene at 25° C. When the dropwise addition has ended, the temperature is slowly increased to 140° C. and the mixture is heated under reflux for 2.5 hours. It is cooled and the solvent and excess chlorosulfonyl isocyanate are removed on a rotary evaporator. The yellow oil which remains (5.4 g=1004 of theory) is used without further purification. When the dropwise addition the mixture is heated under reflux for 2.5 hours It is cooled the solvent and excess chlorosulfonyl isocyanate are removed on a rotary evaporator is used without further purification

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

実験手順: A mixture of 57.1 g (0.31 mole) of 2-hydroxy-3-methoxybenzoic acid, methyl ester, 95.5 g (0.69 mole) of anhydrous potassium carbonate, and 23.9 ml (28.5 g; 0.38 mole) of chloroacetonitrile in 260 ml of N,N-dimethylformamide is heated on the steam bath for three hours. The mixture is cooled, added to 1700 g of ice/water, stirred for 1 hour, and the precipitated crude product is filtered and washed with water. Recrystallization from aqueous methanol yields 52.5 g 77% yield) of the 2-cyanoethoxy-3-methoxybenzoic acid, methyl ester, mp 77°-78° C. (See U.S. Pat. No. 4,420,476 for mp of 74°-75° C.) is heated on the steam bath for three hours The mixture is cooled the precipitated crude product is filtered washed with water Recrystallization from aqueous methanol

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

実験手順: A mixture of 57.1 g (0.31 mole) of 2-hydroxy-3-methoxybenzoic acid, methyl ester, 95.5 g (0.69 mole) of anhydrous potassium carbonate, and 23.9 ml (28.5 g; 0.38 mole) of chloroacetonitrile in 260 ml of N,N-dimethylformamide is heated on the steam bath for three hours. The mixture is cooled, added to 1700 g of ice/water, stirred for 1 hour, and the precipitated crude product is filtered and washed with water. Recrystallization from aqueous methanol yields 52.5 g 77% yield) of the 2-cyanoethoxy-3-methoxybenzoic acid, methyl ester, mp 77°-78° C. (See U.S. Pat. No. 4,420,476 for mp of 74°-75° C.) is heated on the steam bath for three hours The mixture is cooled the precipitated crude product is filtered washed with water Recrystallization from aqueous methanol

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

実験手順: To a solution of methyl 3-methoxysalicylate (1.0 g, 5.49 mmol) in 5 ml tetrahydrofuran and 5 ml dimethylformamide was added sequentially at room temperature, benzyl alcohol (0.71 ml, 6.86 mmol), triphenylphosphine (2.16 g, 8.23 mmol) and diethyl azodicarboxylate (1.3 ml, 8.23 mmol). The reaction solution was stirred at room temperature overnight, then ethyl acetate was added and the resulting solution was washed sequentially with water and brine. The ethyl acetate solution was dried over anhydrous sodium sulfate and concentrated to dryness in vacuo. The residue was triturated with diethyl ether and filtered to remove triphenylphosphine oxide. The ether solution was concentrated to dryness in vacuo and the residue was purified by column chromatography on silica gel, eluting with 95:5 hexane/ethyl acetate, yielding the title compound as an oil (870 mg 58% yield). MS (M+1)+273.1 the resulting solution was washed sequentially with water and brine The ethyl acetate solution was dried over anhydrous sodium sulfate concentrated to dryness in vacuo The residue was triturated with diethyl ether filtered to remove triphenylphosphine oxide The ether solution was concentrated to dryness in vacuo the residue was purified by column chromatography on silica gel eluting with 95:5 hexane/ethyl acetate

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

実験手順: 2-(2-Methoxy-6-methoxycarbonylphenoxy)-1-nitrobenzene (1.24 g, 82%) was prepared from methyl 3-methoxysalicylate (1.0 g, 5.5 mmol) and 1-fluoro-2-nitrobenzene (0.71 g, 5.0 mmol) following the general procedure A. This compound was reduced to 2-(2-methoxy-6-methoxycarbonylphenoxy)aniline (0.89 g, 80%) following the general procedure C. N-[2-(2-Methoxy-6-methoxycarbonylphenoxy)phenyl]-N′-(thiazol-2-yl)urea (143 mg, 72%) was prepared from 2-(2-methoxy-6-methoxycarbonylphenoxy)aniline (136 mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

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

実験手順: 2-(2-Methoxy-6-methoxycarbonylphenoxy)-1-nitrobenzene (1.24 g, 82%) was prepared from methyl 3-methoxysalicylate (1.0 g, 5.5 mmol) and 1-fluoro-2-nitrobenzene (0.71 g, 5.0 mmol) following the general procedure A. This compound was reduced to 2-(2-methoxy-6-methoxycarbonylphenoxy)aniline (0.89 g, 80%) following the general procedure C. N-[2-(2-Methoxy-6-methoxycarbonylphenoxy)phenyl]-N′-(thiazol-2-yl)urea (143 mg, 72%) was prepared from 2-(2-methoxy-6-methoxycarbonylphenoxy)aniline (136 mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

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

実験手順: 2-(2-Methoxy-6-methoxycarbonylphenoxy)-1-nitrobenzene (1.24 g, 82%) was prepared from methyl 3-methoxysalicylate (1.0 g, 5.5 mmol) and 1-fluoro-2-nitrobenzene (0.71 g, 5.0 mmol) following the general procedure A. This compound was reduced to 2-(2-methoxy-6-methoxycarbonylphenoxy)aniline (0.89 g, 80%) following the general procedure C. N-[2-(2-Methoxy-6-methoxycarbonylphenoxy)phenyl]-N′-(thiazol-2-yl)urea (143 mg, 72%) was prepared from 2-(2-methoxy-6-methoxycarbonylphenoxy)aniline (136 mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

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

実験手順: 2-(2-Methoxy-6-methoxycarbonylphenoxy)-1-nitrobenzene (1.24 g, 82%) was prepared from methyl 3-methoxysalicylate (1.0 g, 5.5 mmol) and 1-fluoro-2-nitrobenzene (0.71 g, 5.0 mmol) following the general procedure A. This compound was reduced to 2-(2-methoxy-6-methoxycarbonylphenoxy)aniline (0.89 g, 80%) following the general procedure C. N-[2-(2-Methoxy-6-methoxycarbonylphenoxy)phenyl]-N′-(thiazol-2-yl)urea (143 mg, 72%) was prepared from 2-(2-methoxy-6-methoxycarbonylphenoxy)aniline (136 mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

反応条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3.4 g (0.024 mol) of chlorosulfonyl isocyanate are added dropwise to a solution of 3.6 g (0.02 mol) of methyl 3-methoxy-salicylate in 20 ml of xylene at 25° C. When the dropwise addition has ended, the temperature is slowly increased to 140° C. and the mixture is heated under reflux for 2.5 hours. It is cooled and the solvent and excess chlorosulfonyl isocyanate are removed on a rotary evaporator. The yellow oil which remains (5.4 g=1004 of theory) is used without further purification. When the dropwise addition the mixture is heated under reflux for 2.5 hours It is cooled the solvent and excess chlorosulfonyl isocyanate are removed on a rotary evaporator is used without further purification

反応条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3.4 g (0.024 mol) of chlorosulfonyl isocyanate are added dropwise to a solution of 3.6 g (0.02 mol) of methyl 3-methoxy-salicylate in 20 ml of xylene at 25° C. When the dropwise addition has ended, the temperature is slowly increased to 140° C. and the mixture is heated under reflux for 2.5 hours. It is cooled and the solvent and excess chlorosulfonyl isocyanate are removed on a rotary evaporator. The yellow oil which remains (5.4 g=1004 of theory) is used without further purification. When the dropwise addition the mixture is heated under reflux for 2.5 hours It is cooled the solvent and excess chlorosulfonyl isocyanate are removed on a rotary evaporator is used without further purification

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

実験手順: A mixture of 57.1 g (0.31 mole) of 2-hydroxy-3-methoxybenzoic acid, methyl ester, 95.5 g (0.69 mole) of anhydrous potassium carbonate, and 23.9 ml (28.5 g; 0.38 mole) of chloroacetonitrile in 260 ml of N,N-dimethylformamide is heated on the steam bath for three hours. The mixture is cooled, added to 1700 g of ice/water, stirred for 1 hour, and the precipitated crude product is filtered and washed with water. Recrystallization from aqueous methanol yields 52.5 g 77% yield) of the 2-cyanoethoxy-3-methoxybenzoic acid, methyl ester, mp 77°-78° C. (See U.S. Pat. No. 4,420,476 for mp of 74°-75° C.) is heated on the steam bath for three hours The mixture is cooled the precipitated crude product is filtered washed with water Recrystallization from aqueous methanol

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

実験手順: 2-(2-Methoxy-6-methoxycarbonylphenoxy)-1-nitrobenzene (1.24 g, 82%) was prepared from methyl 3-methoxysalicylate (1.0 g, 5.5 mmol) and 1-fluoro-2-nitrobenzene (0.71 g, 5.0 mmol) following the general procedure A. This compound was reduced to 2-(2-methoxy-6-methoxycarbonylphenoxy)aniline (0.89 g, 80%) following the general procedure C. N-[2-(2-Methoxy-6-methoxycarbonylphenoxy)phenyl]-N′-(thiazol-2-yl)urea (143 mg, 72%) was prepared from 2-(2-methoxy-6-methoxycarbonylphenoxy)aniline (136 mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.