Category: 40872-87-5

Application of 40872-87-5,Some common heterocyclic compound, 40872-87-5, name is Methyl 3-amino-4-chlorobenzoate, molecular formula is C8H8ClNO2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

To a solution of methyl 3-amino-4-chlorobenzoate (3.00 g, 16.2 mmol) and l-(morpholin-4- yl)cyclopropanecarboxylic acid hydrochloride (1:1) (example 65A, 6.71 g, 32.3 mmol, 2 equiv) in DMF (50 mL) was added (benzotriazol-l-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PYBOP, 16.8 g, 32.3 mmol, 2 equiv) and diisopropylethylamine (14.1 mL, 80.8 mmol, 5 equiv). The resulting mixture was stirred at room temperature for 3 days. (Benzotriazol-1- yloxy)tripyrrolidinophosphonium hexafluorophosphate (PYBOP, 16.8 g, 32.3 mmol, 2 equiv) and diisopropylethylamine (14.1 mL, 80.8 mmol, 5 equiv) were added and the resulting mixture was stirred at 60 C over night. The mixture was concentrated under reduced pressure, was then dissolved in dichloromethane, was washed with IN aqueous hydrogen chloride solution and saturated, aqueous sodium bicarbonate solution, was dried over sodium sulfate and concentrated under reduced pressure. The remaining solids were then triturated with ethanol (40 mL), and the resulting mixture was stirred for 30 minutes. The remaining solids were removed by filtration, washed with ethanol, and were dried at 50 C under reduced pressure. The remaining solids were then triturated with ethanol (70 mL), and the resulting mixture was stirred under reflux. After cooling to room temperature, the remaining solids were removed by filtration, washed with ethanol, and were dried at 50 C under reduced pressure to give the title compound (3.60 g). LC-MS (Method 4): Rt= 1.23 min; MS (ESIpos): m/z = 339 [M+H]+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Methyl 3-amino-4-chlorobenzoate, its application will become more common.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; THEDE, Kai; SCOTT, William Johnston; BENDER, Eckhard; GOLZ, Stefan; HAeGEBARTH, Andrea; LIENAU, Philip; PUEHLER, Florian; BASTING, Daniel; SCHNEIDER, Dirk; MOeWES, Manfred; WO2014/147182; (2014); A2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Electric Literature of 40872-87-5, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 40872-87-5, name is Methyl 3-amino-4-chlorobenzoate, This compound has unique chemical properties. The synthetic route is as follows.

In one example of the inventive process, the reaction was conducted with methyl 3-amino-4-chloro-benzoate and 1-cyclopentyl-2-pyridinyl acetylene as the starting materials (Scheme 7). Suitable choices of ligand, base and solvent was important for obtaining satisfactory results as shown in Table 1. Several ligands were examined. It was found that the reaction proceeded smoothly to afford the desired indole product when using either ligand 4a, 4b or 5 in the presence of n-Bu4N+OAc-. The major side-reaction was homocoupling of the arylchloride via double amination (entries 1-3). The proper choice of base, solvent, temperature, and concentration was important to minimize the formation of the amination byproduct and also maximize the desired regioselectivity. By using inorganic bases such as K2CO3, a cleaner reaction could be obtained than by using n-Bu4N+OAc- as base. When a ferrocene ligand such as bis(diisopropylphosphino)ferrocene was employed, in combination with K2CO3 as base, the indolization of 2-chloroaniline with the internal acetylene completed rapidly, providing the product in high purity and regioselectivity (entry 4). Addition of LiCl or LiI as additive did not improve the yield. Instead, it slowed down the reaction (entries 5-6). With reduced catalyst loading (5 mol %), the reaction also proceeded smoothly and cleanly (entry 7). Changing the ratio of ligand to palladium acetate from 2:1 to 1:1 prolonged the reaction time (entry 8). Using K2CO3 as base, ligands 4a, 4b or 6 also afforded good results (entries 9-10). The wavelength used was 240 nm. TABLE I Base Time Entry (Scale) (eq) Catalyst (h) Result* 1 (100 mg) n-Pd(OAc)2 (10%) 4 Complete conversion of Bu4N+OAc- 2-(Di-t- starting material, giving 45 (2.5 eq) butylphosphino)- area % product and 33 biphenyl (40%) area % byproduct. 2 (100 mg) n-Pd(OAc)2 (10%) 3 Ratio of the desired product Bu4N+OAc- 1,1′- to starting material (2.5 eq) Bis(diphenylphosphino) (cholroaniline) was 5:1, ferrocene(20%) about 35 area % unknown impurities. The ratio of the regioisomers was 9:1. 3 (200 mg) n-Pd(OAc)2 (10%) 14 Complete conversion of the Bu4N+OAc- 1,1′-Bis(di-i- starting material, about 35 (2.5 eq) propylphosphino) area % of unknown ferrocene(20%) impurities. The ratio of the regioisomers was 9:1. 28% isolated yield was obtained through column chromatography for two steps. 4 (100 mg)K2CO3 (2.5 eq)Pd(OAc)2 (10%) 3 Complete conversion of the 1,1′-Bis(di-i- starting material. The propylphosphino) desired product was formed ferrocene(20%) in 88 area % purity. The ratio of the regioisomers was 20:1. 5 (100 mg)K2CO3 (2.5 eq)Pd(OAc)2 (10%) 5 Ratio of the desired product 1,1′-Bis(di-i- to the starting material was LiCl (1 eq) propylphosphino) 14:1. The ratio of the ferrocene(20%) regioisomers was 19:1. 6 (100 mg)K2CO3 (2.5 eq)Pd(OAc)2 (10%) 5 The ratio of the desired 1,1′-Bis(di-i- product to the starting LiI (1 eq) propylphosphino) material was 1.6:1. ferrocene(20%) 7 (100 mg)K2CO3 (2.5 eq)Pd(OAc)2 (5%) 14 The ratio of the desired 1,1′-Bis(di-i- product to the starting propylphosphino) material was 5:1. The ratio ferrocene(10%) of regioisomers was 18:1. 8 (100 mg)K2CO3 (2.5 eq)Pd(OAc)2 (5%) 14 The ratio of the desired 1,1′-Bis(di-i- product to the starting propylphosphino) material was 2.5:1. The ferrocene(6%) ratio of regioisomers was 19:1. 9 (100 mg)K2CO3 (2.5 eq)Pd(OAc)2 (5%) 14 Complete conversion of the 2-(Di-t- starting material, with about butylphosphino)- 20 area % impurities. The biphenyl (10%) ratio of the regioisomers was 20:1. 10 (100 mg)K2CO3 (2.5 eq)Pd(OAc)2 (5%) 14 The ratio of the desired Tricyclohexylphosphine product to the starting (10%) material was 4:1. Ratio of the regioisomers was 18:1. *Ratios of product were measured by HPLC analysis

The chemical industry reduces the impact on the environment during synthesis Methyl 3-amino-4-chlorobenzoate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Boehringer Ingelheim International GmbH; US2005/209465; (2005); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Application of 40872-87-5, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 40872-87-5, name is Methyl 3-amino-4-chlorobenzoate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

EXAMPLE 3 Synthesis of 3-cyclopentyl-1-methyl-2-pyridin-2-yl-1H-indole-6-carboxylic acid methyl ester (13) A 100 mL three neck flask equipped with a thermocouple, condenser and stir bar was purged with argon. 3-Amino-4-chlorobenzoic acid methyl ester (5.0 g, 26.94 mmol), 2-cyclopentylethynyl-pyridine (5.528 g, 32.33 mmol), Pd(OAc)2 (181 mg, 0.81 mmol), DtBPF (767 mg, 1.62 mmol), K2CO3 (9.29 g, 67.35 mmol) and NMP (25 mL) were then charged. The reaction was heated to 130 C. and monitored by HPLC. The reaction was complete after 6 hours. The reaction was cooled to room temperature. DMC (11.4 mL, 134.69 mmol) and tetrabutylammonium bromide (TBAB) (0.868 g, 2.69 mmol) were added. The mixture heated to 130 C. HPLC showed less than 3% starting material remaining after 4.5 h. The mixture was filtered through a pad of diatomaceous earth. The black cake was washed with i-PrOAc (50 mL). Solution yield of this mixture was 78%. The crude product residue was dissolved in i-PrOAc (50 mL). The solution was washed with 0.3 N aqueous HCl three times (20 mL, then 2*15 mL). The organic phase was concentrated under vacuum. Propanol, water and 50% NaOH were added to the above residue. The reaction was heated to 90 C. for 1 h. HPLC showed that the reaction was complete. After the mixture was cooled to 50-60 C., diatomaceous earth and activated carbon were added. The mixture was stirred at 50 C. for 30 min and filtered to a 100 mL three neck flask through a pad of diatomaceous earth. The wet cake was washed with 18 mL of water/1-propanol 9/1. The mixture was then heated to 50 C. Acetic acid was added dropwise at this temperature. Precipitation was observed upon the addition. The suspension was then heated to reflux and held for 30 min. The mixture was slowly cooled to room temperature for 2 hours. The precipitate that formed was filtered. The wet cake was washed with 10 mL 1-propanol/water (2:1). The yellow solid was dried under vacuum for 2 days. 5.6 g product was obtained. The yield was 62% for three steps with 99.32 A % purity. 1H NMR (300 MHz, DMSO-d6) delta 8.80 (d, J=3.0 Hz, 1H), 8.14 (s, 1H), 8.00 (m, 1H), 7.77 (d, J=6.0 Hz, 1H), 7.69 (d, J=9.0 Hz, 1H), 7.59 (d, J=6.0 Hz, 1H), 7.50 (m, 1H), 3.89 (s, 3H), 3.70 (s, 3H), 3.17-3.11 (m, 1H), 1.90-1.60 (m, 8H).

The synthetic route of Methyl 3-amino-4-chlorobenzoate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Boehringer Ingelheim International GmbH; US2005/209465; (2005); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Reference of 40872-87-5, These common heterocyclic compound, 40872-87-5, name is Methyl 3-amino-4-chlorobenzoate, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

EXAMPLE 16: 4-Chloro-3-(cyclohexylaminocarbonylamino)benzoylguanidine hydrochloride was prepared from methyl 4-chloro-3-aminobenzoate and cyclohexyl isocyanate in accordance with variants 3 and 2 B. (Benzoic acid ester intermediate: colorless crystals, m.p. 158 C.) Colorless crystals, m.p. 223 C.

Statistics shows that Methyl 3-amino-4-chlorobenzoate is playing an increasingly important role. we look forward to future research findings about 40872-87-5.

Reference:
Patent; Hoechst Aktiengesellschaft; US5559153; (1996); A;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 40872-87-5, name is Methyl 3-amino-4-chlorobenzoate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Computed Properties of C8H8ClNO2

To an ice-cold aqueous solution of concentrated hydrochloric acid (30 mL) was added compound 2 (7.4 g, 40 mmol), followed by the dropwise addition of sodium nitrite (3.036 g, 44.0 mmol) in distilled water (5 mL). After 0.5 h of stirring at 0 C, tin(II) chloride (18.05 g, 80 mmol) in concentrated hydrochloric acid (30 mL) was added dropwise to the above solution. The reaction was stirred for 4 h at 0 C and filtered and successively washed with concentrated hydrochloric acid (15 mL). The precipitate was dissolved in distilled water and filtered. When the filtrate was adjusted to pH 13 by adding 4 mol/L sodium hydroxide under stirring, a large amount of solid formed and was filtered and dried to obtain compound 3. White solid, yield: 63.9%, m.p.132-133 C. 1H NMR (400 MHz, CDCl3) delta 7.76 (s, 1H, Ph-H), 7.40 (d, J = 8.2 Hz, 1H, Ph-H), 7.35 – 7.23 (m, 1H, Ph-H), 5.81 (s, 1H, NH), 3.91 (s, 3H, OCH3), 3.67 (s, 2H, NH2).

The synthetic route of 40872-87-5 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Li, Feng-Yun; Wang, Yuan-Hong; Liu, Jing-Bo; Li, Yu-Xin; Li, Zheng-Ming; Bioorganic and Medicinal Chemistry; vol. 27; 5; (2019); p. 769 – 776;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Application of 40872-87-5,Some common heterocyclic compound, 40872-87-5, name is Methyl 3-amino-4-chlorobenzoate, molecular formula is C8H8ClNO2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

To a mixture of methyl 3-amino-4-chlorobenzoate (10 g, 54 mmol) and aqueous HC1 solution (12 M, 15 mL) in water (80 mL) at 0 C was added dropwise a solution of NaNO2 (4.5 g, 60 mmol) in water (18 mL) at 0 C. The reaction was stirred for 30 mm at 0 C and then added dropwise to a sluny of CuCN (4.9 g, 54 mmol) and KCN (6.0 g, 92 mmol) in water (40 mL), while maintaining the temperature between 5-10 C. The reaction mixture was stined at 10 C for 30 mm and then heated at 80 C for 1 h. After cooling, the mixture was extracted with DCM. The organic layer was washed with brine, dried over Na2504 and then concentrated to afford the title compound. MS: m/z = 196.0 (M + 1). ?H NMR (400 MHz, CDC13) oe 8.34 (d, J 2.0 Hz, 1H), 8.17-8.20 (m, 1H), 7.61 (d,J= 8.4 Hz, 1H), 3.96 (s, 3H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Methyl 3-amino-4-chlorobenzoate, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; STUMP, Craig A.; CHEN, Yi Heng; LIU, Ping; MENG, Dongfang; WU, Jane; LI, Chun Sing; QI, Zhiqi; (163 pag.)WO2016/161572; (2016); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics