4-氨基-3,5-二氯苯甲酸乙酯

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Part A: To a stirred suspension of 4.33 g (18.5 mmol) of ethyl 4-amino-3,5-dichlorobenzoate in 8 mL conc. HCl at 0° C. was added a solution of 1.28 g (18.5 mmol) of sodium nitrite in 8 mL water dropwise. After stirring at 0° C. for 45 min, a solution of 12.52 g (55.5 mmol) tin(II) chloride in 14 ML conc. HCl was added dropwise. The reaction was sealed and placed in the refrigerator for 18 h. The solid was collected by suction filtration, washed with brine and then 2:1 petroleum ether-diethyl ether, treated with 1 N NaOH, and filtered. This solid was dissolved in diethyl ether, acidified with 4 N HCl in dioxane, filtered and washed with diethyl ether to give 2.85 g (54%) of ethyl 3,5-dichloro-4-hydrazinobenzoate hydrochloride, mp 225-227 (dec)° C. Mass Spec.: (CI+) 249 (M+). The reaction was sealed placed in the refrigerator for 18 h The solid was collected by suction filtration washed with brine 2:1 petroleum ether-diethyl ether, treated with 1 N NaOH filtered This solid was dissolved in diethyl ether filtered washed with diethyl ether

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Following the procedure in Rouot et al., in J. Med. Chem., 19, 1049 (1976), 4-amino-3,5-dichlorobenzoic acid ethyl ester (70.2 g., 030 m) is reacted with the product from acetic anhydride (61.3 g., 0.60 m) and formic acid (34.5 g., 0.75 m) to yield the desired 3,5-dichloro-4-formamidobenzoic acid ethyl ester (62.0 g., 0.237 m) in crude yield of 79% with a melting point of 168°-170° C. Reaction of this crude (16.35 g., 0.062 m) with a mixture of thionyl chloride (55.4 g., 0.47 m) and sulfuryl chloride (3.4 g., 0.062 m) leads to the desired 3,5-dichloro-4-dichloromethaniminobenzoic acid ethyl ester (14.65 g., 46 mmol) which distills at 105° C. at 250 mm of Hg after standard workup. It should be noted that this material may solidify on standing. Finally, this distilled dichloromethamine (4.35 g., 0.0138 m) is reacted with ethylene diamine (1.66 g., 0.0276 m), and 10 mL of triethylamine in approximately 25 mL of ethyl acetate for 10 hours. An immediate white precipitate is noted, but stirring is continued overnight to ensure complete reaction. This reaction mixture then is vacuum filtered to yield 5.35 g. of white powder (which is greater than 100% yield, but is probably due to the fact that, in addition to the desired compound, triethylamine hydrochloride as well as the hydrochloride of the desired compound are present at this stage). Recrystallization of the white powder from absolute ethanol produced a white crystalline solid (2.3 g., 0.0076 m) in a yield of 55% with a melting point of 238°-240° C. This compound demonstrates the expected IR absorptions at 3380 (sharp), 3150 (broad), 1710 (sharp), 1660 (sharp and most intense), 1580 (sharp), 1275 (sharp), 1105 cm-1 (sharp).

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Following the procedure in Rouot et al., in J. Med. Chem., 19, 1049 (1976), 4-amino-3,5-dichlorobenzoic acid ethyl ester (70.2 g., 030 m) is reacted with the product from acetic anhydride (61.3 g., 0.60 m) and formic acid (34.5 g., 0.75 m) to yield the desired 3,5-dichloro-4-formamidobenzoic acid ethyl ester (62.0 g., 0.237 m) in crude yield of 79% with a melting point of 168°-170° C. Reaction of this crude (16.35 g., 0.062 m) with a mixture of thionyl chloride (55.4 g., 0.47 m) and a sulfuryl chloride (3.4 g., 0.062 m) leads to the desired 3,5-dichloro-4-dichloromethaniminobenzoic acid ethyl ester (14.65 g., 46 mmol) which distills at 105° C. at 250 mm of Hg after standard workup. It should be noted that this material may solidify on standing. Finally, this distilled dichloromethamine (4.35 g., 0.0138 m) is reacted with ethylene diamine (1.66 g., 0.0276 m), and 10 mL of triethylamine in approximately 25 mL of ethyl acetate for 10 hours. An immediate white precipitate is noted, but stirring is continued overnight to ensure complete reaction. This reaction mixture then is vacuum filtered to yield 5.35 g. of white powder (which is greater than 100% yield, but is probably due to the fact that, in addition to the desired compound, triethylamine hydrochloride as well as the hydrochloride of the desired compound are present at this stage). Recrystallization of the white powder from absolute ethanol produced a white crystalline solid (2.3 g., 0.0076 m) in a yield of 55% with a melting point of 238°-240° C. This compound demonstrates the expected IR absorptions at 3380 (sharp), 3150 (broad), 1710 (sharp), 1660 (sharp and most intense), 1580 (sharp), 1275 (sharp), 1105 cm-1 (sharp).

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Part A: To a stirred suspension of 4.33 g (18.5 mmol) of ethyl 4-amino-3,5-dichlorobenzoate in 8 mL conc. HCl at 0° C. was added a solution of 1.28 g (18.5 mmol) of sodium nitrite in 8 mL water dropwise. After stirring at 0° C. for 45 min, a solution of 12.52 g (55.5 mmol) tin(II) chloride in 14 ML conc. HCl was added dropwise. The reaction was sealed and placed in the refrigerator for 18 h. The solid was collected by suction filtration, washed with brine and then 2:1 petroleum ether-diethyl ether, treated with 1 N NaOH, and filtered. This solid was dissolved in diethyl ether, acidified with 4 N HCl in dioxane, filtered and washed with diethyl ether to give 2.85 g (54%) of ethyl 3,5-dichloro-4-hydrazinobenzoate hydrochloride, mp 225-227 (dec)° C. Mass Spec.: (CI+) 249 (M+). The reaction was sealed placed in the refrigerator for 18 h The solid was collected by suction filtration washed with brine 2:1 petroleum ether-diethyl ether, treated with 1 N NaOH filtered This solid was dissolved in diethyl ether filtered washed with diethyl ether

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Part A: To a stirred suspension of 4.33 g (18.5 mmol) of ethyl 4-amino-3,5-dichlorobenzoate in 8 mL conc. HCl at 0° C. was added a solution of 1.28 g (18.5 mmol) of sodium nitrite in 8 mL water dropwise. After stirring at 0° C. for 45 min, a solution of 12.52 g (55.5 mmol) tin(II) chloride in 14 ML conc. HCl was added dropwise. The reaction was sealed and placed in the refrigerator for 18 h. The solid was collected by suction filtration, washed with brine and then 2:1 petroleum ether-diethyl ether, treated with 1 N NaOH, and filtered. This solid was dissolved in diethyl ether, acidified with 4 N HCl in dioxane, filtered and washed with diethyl ether to give 2.85 g (54%) of ethyl 3,5-dichloro-4-hydrazinobenzoate hydrochloride, mp 225-227 (dec)° C. Mass Spec.: (CI+) 249 (M+). The reaction was sealed placed in the refrigerator for 18 h The solid was collected by suction filtration washed with brine 2:1 petroleum ether-diethyl ether, treated with 1 N NaOH filtered This solid was dissolved in diethyl ether filtered washed with diethyl ether

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:250.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 0.2 mole=49.3 g of ethyl 3,5-dichloro-4-amino-benzoate were initially introduced into an autoclave together with 250 ml of water. The mixture was heated to 250° C. and stirred at this temperature for 2.5 hours. Reaction gas formed was continuously removed to maintain a pressure of about 40 bar. The product was subsequently recovered by steam distillation. 31 g of 2,6-dichloroaniline were obtained, corresponding to a yield of 94%. Reaction gas formed was continuously removed to maintain a pressure of about 40 bar The product was subsequently recovered by steam distillation

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Part A: To a stirred suspension of 4.33 g (18.5 mmol) of ethyl 4-amino-3,5-dichlorobenzoate in 8 mL conc. HCl at 0° C. was added a solution of 1.28 g (18.5 mmol) of sodium nitrite in 8 mL water dropwise. After stirring at 0° C. for 45 min, a solution of 12.52 g (55.5 mmol) tin(II) chloride in 14 mL conc. HCl was added dropwise. The reaction was sealed and placed in the refrigerator for 18 h. The solid was collected by suction filtration, washed with brine and then 2:1 petroleum ether-diethyl ether, treated with 1 N NaOH, and filtered. This solid was dissolved in diethyl ether, acidified with 4 N HCl in dioxane, filtered and washed with diethyl ether to give 2.85 g (54%) of ethyl 3,5-dichloro-4-hydrazinobenzoate hydrochloride, mp 225-227 (dec)° C. Mass Spec.: (CI+) 249 (M+). The reaction was sealed placed in the refrigerator for 18 h The solid was collected by suction filtration washed with brine 2:1 petroleum ether-diethyl ether, treated with 1 N NaOH filtered This solid was dissolved in diethyl ether filtered washed with diethyl ether

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4-Amino-3,5-dichlorobenzoic acid ethyl ester (17.7 g) was dissolved in a mixture of acetic acid (75 mL) and dichloromethane (75 mL) and then methanesulfonic acid (22 mL) was added. 3-Methylbutyl nitrite (10 mL) was added to the solution while the temperature was kept at 0-5° C. After 30 min, mercaptoacetic acid (38 mL) was added at 0-5° C. Then a part of the dichloromethane was removed by distillation which was stopped when the internal temperature of the mixture was 80° C. and this temperature was kept for additional 45 min. The mixture was cooled and the rest of the solvents were evaporated under vacuum. Toluene (300 mL), water (200 mL) and hydrochloric acid (6 M, 80 mL) were added. The organic phase was separated and then extracted with potassium bicarbonate solution (1 M, 200 mL) which was acidified with hydrochloric acid (6M, 50 mL). The product was extracted to toluene (100 mL) which was dried (sodium sulphate) and evaporated to dryness (yield 5.1 g). 1H-NMR (400 MHz, DMSO-d6) d=1.33 (t, J=7.0 Hz, 3H), 3.74 (s, 2H), 4.34 (q, J=7.0 Hz, 2H), 7.97 (s, 2H), 12.5 (b, 1H). was kept at 0-5° C Then a part of the dichloromethane was removed by distillation which was 80° C. this temperature was kept for additional 45 min The mixture was cooled the rest of the solvents were evaporated under vacuum Toluene (300 mL), water (200 mL) and hydrochloric acid (6 M, 80 mL) were added The organic phase was separated extracted with potassium bicarbonate solution (1 M, 200 mL) which The product was extracted to toluene (100 mL) which was dried (sodium sulphate) evaporated to dryness (yield 5.1 g)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Following the procedure in Rouot et al., in J. Med. Chem., 19, 1049 (1976), 4-amino-3,5-dichlorobenzoic acid ethyl ester (70.2 g., 030 m) is reacted with the product from acetic anhydride (61.3 g., 0.60 m) and formic acid (34.5 g., 0.75 m) to yield the desired 3,5-dichloro-4-formamidobenzoic acid ethyl ester (62.0 g., 0.237 m) in crude yield of 79% with a melting point of 168°-170° C. Reaction of this crude (16.35 g., 0.062 m) with a mixture of thionyl chloride (55.4 g., 0.47 m) and sulfuryl chloride (3.4 g., 0.062 m) leads to the desired 3,5-dichloro-4-dichloromethaniminobenzoic acid ethyl ester (14.65 g., 46 mmol) which distills at 105° C. at 250 mm of Hg after standard workup. It should be noted that this material may solidify on standing. Finally, this distilled dichloromethamine (4.35 g., 0.0138 m) is reacted with ethylene diamine (1.66 g., 0.0276 m), and 10 mL of triethylamine in approximately 25 mL of ethyl acetate for 10 hours. An immediate white precipitate is noted, but stirring is continued overnight to ensure complete reaction. This reaction mixture then is vacuum filtered to yield 5.35 g. of white powder (which is greater than 100% yield, but is probably due to the fact that, in addition to the desired compound, triethylamine hydrochloride as well as the hydrochloride of the desired compound are present at this stage). Recrystallization of the white powder from absolute ethanol produced a white crystalline solid (2.3 g., 0.0076 m) in a yield of 55% with a melting point of 238°-240° C. This compound demonstrates the expected IR absorptions at 3380 (sharp), 3150 (broad), 1710 (sharp), 1660 (sharp and most intense), 1580 (sharp), 1275 (sharp), 1105 cm-1 (sharp).

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Following the procedure in Rouot et al., in J. Med. Chem., 19, 1049 (1976), 4-amino-3,5-dichlorobenzoic acid ethyl ester (70.2 g., 030 m) is reacted with the product from acetic anhydride (61.3 g., 0.60 m) and formic acid (34.5 g., 0.75 m) to yield the desired 3,5-dichloro-4-formamidobenzoic acid ethyl ester (62.0 g., 0.237 m) in crude yield of 79% with a melting point of 168°-170° C. Reaction of this crude (16.35 g., 0.062 m) with a mixture of thionyl chloride (55.4 g., 0.47 m) and a sulfuryl chloride (3.4 g., 0.062 m) leads to the desired 3,5-dichloro-4-dichloromethaniminobenzoic acid ethyl ester (14.65 g., 46 mmol) which distills at 105° C. at 250 mm of Hg after standard workup. It should be noted that this material may solidify on standing. Finally, this distilled dichloromethamine (4.35 g., 0.0138 m) is reacted with ethylene diamine (1.66 g., 0.0276 m), and 10 mL of triethylamine in approximately 25 mL of ethyl acetate for 10 hours. An immediate white precipitate is noted, but stirring is continued overnight to ensure complete reaction. This reaction mixture then is vacuum filtered to yield 5.35 g. of white powder (which is greater than 100% yield, but is probably due to the fact that, in addition to the desired compound, triethylamine hydrochloride as well as the hydrochloride of the desired compound are present at this stage). Recrystallization of the white powder from absolute ethanol produced a white crystalline solid (2.3 g., 0.0076 m) in a yield of 55% with a melting point of 238°-240° C. This compound demonstrates the expected IR absorptions at 3380 (sharp), 3150 (broad), 1710 (sharp), 1660 (sharp and most intense), 1580 (sharp), 1275 (sharp), 1105 cm-1 (sharp).