Benzoic acid, 2-amino-4,5-bis(2-methoxyethoxy)-, ethyl ester

General procedure: A mixture of the organic nitro compound (1.0 mmol), NH2NH2·H2O (2.5 equiv.) and H2O2-treated AC powder (50 wtpercent) in DMF (1.5 mL) was stirred vigorously magnetically at 100 °C. The reaction was monitored by LC–MS or GC–MS. On completion the reaction mixture was filtered to remove the catalyst. The combined organic mixture material was dried using anhydrous Na2SO4 and filtered. The solvent was removed under reduced pressure to obtain the products. All the compounds were known and characterised by their The reaction vessel was charged with 260g of Compound II prepared according to the method of and 3000ml of absolute ethanol. 50g of sodium borohydride was added under stirring to control the reaction temperature at 30-40 ° C. The progress of the reaction was monitored by TLC. After about 4 hours, Filtration, the filtrate was concentrated under reduced pressure, evaporated and evaporated to recover the set of ethanol to the next batch of reduction reaction section, non-condensing gas into the exhaust absorption device. The concentrate was collected and confirmed by structure to give 232.8 g of compound III in a yield of 98.1percent. The purity was 99.9percent by HPLC.Compound (iv) (196 · 4g) was dissolved in absolute ethanol (3000mL) was added Raney Ni (39 · 3g), hydrogen gas is setChange three times. In a hydrogen atmosphere, heated to 40 ° C for 20 hours, the HPLC detector material is less than 1percent, cooled to 25 ° C. Filtration, With anhydrous ethanol (701 ^) rinse, spin dry ethanol to give compound (¥) (171.18), yield 95.5percent, purity> 95percent[Synthesis Example 3]; (Synthesis of ethyl 2-amino-4, 5-bis(2-methoxyethoxy)-benzoate); In a 20 L-volume glass reaction vessel equipped with a stirrer, a thermometer and a reflux condenser, 2, 328 g (6.78 moles) of the ethyl 4, 5-bis(2-methoxyethoxy)-2-nitrobenzoate prepared in the Synthesis Example 2, 2 wt.percent platinum per 118 g of carbon (50 wt.percent product, N.E. Chemcat Corporation, 6.0 mmoles in terms of platinum metallic atom) and 9, 440 mL of methanol were placed. The mixture was allowed to react at 50 to 60°C for 6 hours in an atmosphere of hydrogen while stirring. After the reaction was complete, the reaction solution was cooled to room temperature, and filtered. The filtrate was concentrated under reduced pressure to obtain 1, 960 g of ethyl 2-amino-4, 5-bis(2-methoxyethoxy)benzoate as an orange liquid (isolation yield: 92percent).Subsequently, 4, 5-bis-(2-methoxy-ethoxy)-2-nitro-benzoic acid ethyl ester (3.0 mg) produced by the above process was dissolved in methanol, and platinum oxide (250 mg) was added to the solution at room temperature. The air in the reaction system was replaced by hydrogen, and the mixture was then stirred for one hr. After the completion of the reaction, the atmosphere in the reaction system was replaced by nitrogen. The reaction solution was filtered through Celite to remove platinum oxide. The filtrate was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a hexane-acetone system to give 2-amino-4, 5-bis-(2-methoxy-ethoxy)-benzoic acid ethyl ester (compound A) (2.5 g, yield 92percent).2) catalytic hydrogenation reaction: 200 g of the nitrification product obtained in the previous step is dissolved in 5 L of anhydrous methanol, and then added15g of Pt/C catalyst with Pt content of 10percent is fully stirred and mixed to form material IV, H2 is used as material V, and the slurry pump is adjusted.The flow rate is such that the flow rate of the material IV is 42.0 g/min, the flow rate of the gas flow meter is adjusted to 600 ml/min, the molar ratio of the nitrification product to H2 is 1:3.4, the reaction temperature is 90 ° C, and the temperature of the cooling module is 25 ° C. , the reaction residence time is 35s, the reactionThe pressure is 1.5Mpa, and the reaction liquid flowing out from the outlet of the cooling module is collected for post-treatment, and the post-treatment refers to filtration and recovery.Catalyst Pt/C, the organic solvent was recovered by distillation under reduced pressure, and the residue was added with 1.2 L of acetone to stir the solvent, and 450 ml of concentrated salt was added.Acid, stirring and crystallization for 1h, filtration, the filter cake is put into 2L of water, adding 2mol / L NaOH solution to adjust the pH of the system8.0 or so, 2L of ethyl acetate was added twice, each time 1 L of ethyl acetate was added, and the organic phase was combined and dried over anhydrous sodium sulfateAfter drying solvent is recovered by distillation under reduced pressure to give the product amino 161.12g, yield 88.27percent, purity 99.59percent.(2) General procedure: A mixture of the organic nitro compound (1.0 mmol), NH2NH2·H2O (2.5 equiv.) and H2O2-treated AC powder (50 wt%) in DMF (1.5 mL) was stirred vigorously magnetically at 100 C. The reaction was monitored by LC-MS or GC-MS. On completion the reaction mixture was filtered to remove the catalyst. The combined organic mixture material was dried using anhydrous Na2SO4 and filtered. The solvent was removed under reduced pressure to obtain the products. All the compounds were known and characterised by their 1H NMR and MS spectra and comparison with literature data.The reaction vessel was charged with 260g of Compound II prepared according to the method of and 3000ml of absolute ethanol. 50g of sodium borohydride was added under stirring to control the reaction temperature at 30-40 C. The progress of the reaction was monitored by TLC. After about 4 hours, Filtration, the filtrate was concentrated under reduced pressure, evaporated and evaporated to recover the set of ethanol to the next batch of reduction reaction section, non-condensing gas into the exhaust absorption device. The concentrate was collected and confirmed by structure to give 232.8 g of compound III in a yield of 98.1%. The purity was 99.9% by HPLC.Compound (iv) (196 · 4g) was dissolved in absolute ethanol (3000mL) was added Raney Ni (39 · 3g), hydrogen gas is setChange three times. In a hydrogen atmosphere, heated to 40 C for 20 hours, the HPLC detector material is less than 1%, cooled to 25 C. Filtration, With anhydrous ethanol (701 ^) rinse, spin dry ethanol to give compound (¥) (171.18), yield 95.5%, purity> 95%[Synthesis Example 3]; (Synthesis of ethyl 2-amino-4, 5-bis(2-methoxyethoxy)-benzoate); In a 20 L-volume glass reaction vessel equipped with a stirrer, a thermometer and a reflux condenser, 2, 328 g (6.78 moles) of the ethyl 4, 5-bis(2-methoxyethoxy)-2-nitrobenzoate prepared in the Synthesis Example 2, 2 wt.% platinum per 118 g of carbon (50 wt.% product, N.E. Chemcat Corporation, 6.0 mmoles in terms of platinum metallic atom) and 9, 440 mL of methanol were placed. The mixture was allowed to react at 50 to 60C for 6 hours in an atmosphere of hydrogen while stirring. After the reaction was complete, the reaction solution was cooled to room temperature, and filtered. The filtrate was concentrated under reduced pressure to obtain 1, 960 g of ethyl 2-amino-4, 5-bis(2-methoxyethoxy)benzoate as an orange liquid (isolation yield: 92%).Subsequently, 4, 5-bis-(2-methoxy-ethoxy)-2-nitro-benzoic acid ethyl ester (3.0 mg) produced by the above process was dissolved in methanol, and platinum oxide (250 mg) was added to the solution at room temperature. The air in the reaction system was replaced by hydrogen, and the mixture was then stirred for one hr. After the completion of the reaction, the atmosphere in the reaction system was replaced by nitrogen. The reaction solution was filtered through Celite to remove platinum oxide. The filtrate was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a hexane-acetone system to give 2-amino-4, 5-bis-(2-methoxy-ethoxy)-benzoic acid ethyl ester (compound A) (2.5 g, yield 92%).2) catalytic hydrogenation reaction: 200 g of the nitrification product obtained in the previous step is dissolved in 5 L of anhydrous methanol, and then added15g of Pt/C catalyst with Pt content of 10% is fully stirred and mixed to form material IV, H2 is used as material V, and the slurry pump is adjusted.The flow rate is such that the flow rate of the material IV is 42.0 g/min, the flow rate of the gas flow meter is adjusted to 600 ml/min, the molar ratio of the nitrification product to H2 is 1:3.4, the reaction temperature is 90 C, and the temperature of the cooling module is 25 C. , the reaction residence time is 35s, the reactionThe pressure is 1.5Mpa, and the reaction liquid flowing out from the outlet of the cooling module is collected for post-treatment, and the post-treatment refers to filtration and recovery.Catalyst Pt/C, the organic solvent was recovered by distillation under reduced pressure, and the residue was added with 1.2 L of acetone to stir the solvent, and 450 ml of concentrated salt was added.Acid, stirring and crystallization for 1h, filtration, the filter cake is put into 2L of water, adding 2mol / L NaOH solution to adjust the pH of the system8.0 or so, 2L of ethyl acetate was added twice, each time 1 L of ethyl acetate was added, and the organic phase was combined and dried over anhydrous sodium sulfateAfter drying solvent is recovered by distillation under reduced pressure to give the product amino 161.12g, yield 88.27%, purity 99.59%.(2) Preparation of Ethyl 2-amino-4, 5-dimethoxyethoxybenzoate 15 Ethyl 2-nitro-4, 5-dimethoxyethoxybenzoate 14 (7 g, 20.40 mmol) is placed in a two-neck bottle of 500 ml, THF (30 ml), water (140 ml) and NH4OH (4 ml, 28~30%) are added, then sodium hydrosulfite (3.88 g, 28.04 mmol) is added, and heat refluxing is carried out for 2 hours. Conc.HCl (4 ml) is added to continue heat refluxing for 2 hours. After reaction is completed and cooled to 5 C., NaOH (18 ml, 20%) is added to adjust pH>9. Extraction is performed by using ethyl acetate (200 ml*2), organic layers are combined to be washed by water (200 ml), and the organic layers is dried by adding anhydrous MgSO4, filtered and concentrated to obtain brown liquid compound 15 (5.34 g, 85.1%). 1H-NMR (CDCl3) spectrum: 1.33 (t, 2H, J=7.1 Hz), 3.41 (s, 6H), 3.68~3.71 (m, 4H), 4.04~4.25 (m, 4H), 4.26 (q, 2H, J=7.1 Hz), 6.14 (s, 1H), 7.42 (s, 1H).1.7 Synthesis of ethyl 6-amino-3, 4-bis(methoxyethoxy)benzoate0.2 mol ethyl 6-nitro-3, 4-bis(methoxyethoxy)benzoate was dissolved in 250 ml methanol, adding 0.5g palladium carbon (10%), into the hydrogen. After 12h the reaction is complete, filtering out palladium-carbon. Revolving off a solvent, be oil, directly used for the next reactionTo the reaction flask was added ethyl 2-amino-4, 5-di-(2-methoxyethoxy)-benzoate 350 g, dimethyl500 mL of amide and 200 g of ammonium formate. The reaction was heated to 160 C and monitored by TLC until ethyl 2-amino-4, 5-di-(2-methoxyethoxy)-benzoate was completely reacted. The temperature is lowered to 0 to 5 C to precipitate, suction filtration, the filter cake is washed with acetone, and dried at 80 C.Compound II (white solid, 232.6 g, yield 79%) was obtained.

Molecular Weight:313.35
XLogP3:1.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:7
Rotatable Bond Count:11
Exact Mass:313.15253745
Monoisotopic Mass:313.15253745
Topological Polar Surface Area:89.2
Heavy Atom Count:22
Complexity:314
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes