Category: 25252-00-0

25252-00-0, A common compound: 25252-00-0, name is 2-Bromo-5-iodobenzoic acid, belongs to iodides-buliding-blocks compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

Oxalyl chloride (13.0 mL) is added to an ice-cold solution of 2-bromo-5-iodo-benzoic acid (49.5 g) in CH2C12 (200 mL). DMF (0.2 mL) is added and the solution is stirred at room temperature for 6 h. Then, the solution is concentrated under reduced pressure and the residue is dissolved in THF (100 mL). The resulting solution is cooled in an ice-bath and L1BH4 (3.4 g) is added in portions. The cooling bath is removed and the mixture is stirred at room temperature for 1 h. The reaction mixture is diluted with THF and treated with 0.1 M hydrochloric acid. Then, the organic layer is separated and the aqueous layer is extracted with ethyl acetate. The combined organic layers are dried (Na2S04) and the solvent is evaporated under reduced pressure to give the crude product. Yield: 47.0 g (99% of theory)

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, 2-Bromo-5-iodobenzoic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BOEHRINGER INGELHEIM VETMEDICA GMBH; REICHE, Dania Birte; JOHNSTON, Laura; MOHREN, Nicole; WO2014/161836; (2014); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

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. 25252-00-0, name is 2-Bromo-5-iodobenzoic acid, This compound has unique chemical properties. The synthetic route is as follows., Product Details of 25252-00-0

Step I: To a stirred solution of 2-bromo-5-iodobenzoic acid (150 g, 458 mmol) in dichloromethane (1500 ml) was added DMF (2.0 ml) followed by oxalylchloride (58.2 ml, 688 mmol) at 0 C in drop wise fashion over the period of 30 min. After complete addition, the reaction mixture was stirred at room temperature for 3h. Volatiles were evaporated under reduced pressure to give 2-bromo-5-iodo-benzoyl chloride (-158 g). The crude product was used for the next step immediately. (Note: The product should not be exposed to air).

According to the analysis of related databases, 25252-00-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; NOVARTIS AG; BEBERNITZ, Gregory Raymond; BOCK, Mark Gary; WO2012/140596; (2012); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Electric Literature of 25252-00-0, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 25252-00-0 as follows.

Part C. 3′-(1-benzyl-6-cyano-1H-indol-3-ylmethyl)-4-carbamoyl-biphenyl-2-carboxylic acid benzyl ester:; 2-Bromo-5-iodobenzoic acid (6.54 g, 20.0 mmol) was dissolved in DMF (70 mL). Potassium bicarbonate (2.2 g, 22.0 mmol) was added, followed by benzyl bromide (2.8 mL, 22.0 mmol). The mixture was stirred at rt under N2 for 12 h. The reaction mixture was poured into water and extracted with EtOAc. The combined organic solution was washed with brine, dried over MgSO4, and concentrated and dried to give 9.05 g of the benzyl ester. The ester (2.3 g, 7.69 mmol), Zn(CN)2 (1.3 g, 11.5 mmol), and Pd[PPh3]4 were dissolved together in 25 mL of DMF. The mixture was de-gassed and heated at 90 C. for 4 h. Reaction mixture was concentrated and purified by chromatography (silica gel, 5% EtOAc in hexane) to give 1.8 g of the benzonitrile. MS: 316.0, 317.9 (M+1)+. The benzonitrile (1.4 g, 4.4 mmol) was dissolved in 15 mL of DMF. The reaction mixture was cooled at 0 C. Potassium carbonate (0.20 g, 1.45 mmol) was added, followed by dropwise addition of 30% hydrogen peroxide solution (1.2 mL). The cooling bath was removed and the mixture was stirred at rt for 12 h. The reaction was quenched with aqueous NaHSO3 and water. The formed precipitate was filtered and dried to give 1.1 g of the desired amide. MS: 334.2, 336.3 (M+1)+. A mixture of the resulting amide (0.2 g, 0.6 mmole), bis(pinacolato)diboron (0.228 g, 0.9 mmol) and anhydrous KOAc (0.18 g, 1.8 mmol) in 2 mL of 1,4-dioxane was purged with argon, then (1,1′)-bis(diphenylphosphino)ferrocene)palladium(II) chloride (20 mg, 0.024 mmol) was added. The resulting mixture was heated in a sealed tube in a microwave reactor at 100 C. for 2 h then left standing overnight at rt. The reaction was diluted with water and extracted 3× with EtOAc. The combined extracts were washed with brine, dried over Na2SO4, filtered and evaporated in vacuo. Chromatography on silica gel (hexane/ethyl acetate 1:1) provided the boronate (0.13 g, 57%). A mixture of this compound, the compound of Part B (0.1 g, 0.25 mmol), and K3PO4 (0.11 g, 0.5 mmol) in 5 mL dioxane was degassed and then treated with tetrakis(triphenylphosphine)palladium(20 mg, 0.017 mmol). The resulting mixture was heated in a 95-100 C. oil bath under N2 for 2 h, then stirred at rt overnight. The reaction mixture was diluted with brine and extracted 3× with EtOAc. The combined extracts were washed with brine then dried over anhydrous Na2CO3, filtered and evaporated. Chromatography on silica gel (hexane/ethyl acetate 1:1) provided the product (0.12 g, 83%) as a light yellow foam. 1H NMR (400 MHz, CDCl3) delta ppm 4.07 (s, 2H) 4.90 (s, 2H) 5.23 (s, 2H) 6.91 (d, J=6.15 Hz, 2H) 7.05 (m, 3H) 7.20 (m, 6H) 7.29 (m, 5H) 7.42 (d, J=7.91 Hz, 1H) 7.51 (d, J=10.99 Hz, 2H) 7.98 (dd, J=8.13, 1.98 Hz, 1H) 8.19 (d, J=2.20 Hz, 1H). LC/MS m/z 576.16 (M+H)+.

According to the analysis of related databases, 25252-00-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Smallheer, Joanne M.; Corte, James R.; US2005/228000; (2005); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Synthetic Route of 25252-00-0, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 25252-00-0 as follows.

2-bromo-5-iodo-benzoic acid (5.0 g, 15.3 mmol) and oxalyl chloride (4.0 mL, 46.5 mmol) were dissolved in dichloromethane (30 mL), then the reaction mixture was cooled to 0 C., and then 2 drops of N, N-dimethylformamide were slowly added. The reaction mixture was naturally warmed up to room temperature and then stirred for 1 hour until the reaction system became clear. The solvent and excess oxalyl chloride were removed under reduced pressure. The resulting residue was dried in vacuo to give 2-bromo-5-iodobenzoyl chloride (5.25 g, a pale yellow oil, yield: nearly 100%).

According to the analysis of related databases, 25252-00-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Jiangsu Hansoh Pharmaceutical Co., Ltd.; ZHONG, Huijuan; LIAO, Jianchun; YU, Hongping; XU, Yaochang; LI, Qing; CHEN, Jianghua; GAO, Peng; TAN, Songliang; WANG, Shaobao; (45 pag.)US2016/222047; (2016); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 25252-00-0 as follows. Recommanded Product: 25252-00-0

Tetrahydrofuran (99.7g) and sodium borohydride (15.2g, 0.4mol) were added to the reaction flask at 10-25C.A solution of 2-bromo-5-iodobenzoic acid (109.4 g, 0.34 mol, prepared in Example 2) in tetrahydrofuran (151 g) was slowly added dropwise.At 10-30C, a solution of sulfuric acid (16.4 g) in tetrahydrofuran (25 g) was added dropwise to the reaction vessel. After the addition was completed, the reaction was performed at room temperature for 2 hours. Then, it was heated to reflux 66C, refluxed for 2 hours, and then lowered to room temperature. 5% hydrochloric acid (235 g) was slowly added dropwise and THF was distilled off under reduced pressure (-0.01 MPa).Add 326.7 g of MTBE and 222.7 g of water to dissolve the solid, cool to 15-25C, separate the layers, and evaporate the organic layer under reduced pressure (-0.095 MPa).Toluene (108.8 g) and water (108.8 g) were added and the mixture was warmed to 60C for 1 h, reduced to 18-22C and filtered. After drying, 89.1 g of an off-white solid product was obtained with a measured content of >99% and a yield of 85.1%.

According to the analysis of related databases, 25252-00-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Jinkai (Liaoning) Chemical Co., Ltd.; Wang Yongcan; Zhang Hong; Li Zhenwei; Zhao Yang; Zhang Guifang; Song Tongji; Hu Zhenzhu; Huang Fengting; (8 pag.)CN107954861; (2018); A;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

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. 25252-00-0, name is 2-Bromo-5-iodobenzoic acid, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 2-Bromo-5-iodobenzoic acid

Step I: To a stirred solution of 2-bromo-5-iodobenzoic acid (150 g, 458 mmol) in dichloromethane (1500 ml) was added DMF (2.0 ml) followed by oxalylchloride (58.2 ml, 688 mmol) at 0 C in drop wise fashion over the period of 30 min. After complete addition, the reaction mixture was stirred at room temperature for 3h. Volatiles were evaporated under reduced pressure to give 2-bromo-5-iodo-benzoyl chloride (-158 g). The crude product was used for the next step immediately. (Note: The product should not be exposed to air).

According to the analysis of related databases, 25252-00-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; NOVARTIS AG; BEBERNITZ, Gregory Raymond; BOCK, Mark Gary; WO2012/140596; (2012); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Electric Literature of 25252-00-0, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 25252-00-0 as follows.

Part C. 3′-(1-benzyl-6-cyano-1H-indol-3-ylmethyl)-4-carbamoyl-biphenyl-2-carboxylic acid benzyl ester:; 2-Bromo-5-iodobenzoic acid (6.54 g, 20.0 mmol) was dissolved in DMF (70 mL). Potassium bicarbonate (2.2 g, 22.0 mmol) was added, followed by benzyl bromide (2.8 mL, 22.0 mmol). The mixture was stirred at rt under N2 for 12 h. The reaction mixture was poured into water and extracted with EtOAc. The combined organic solution was washed with brine, dried over MgSO4, and concentrated and dried to give 9.05 g of the benzyl ester. The ester (2.3 g, 7.69 mmol), Zn(CN)2 (1.3 g, 11.5 mmol), and Pd[PPh3]4 were dissolved together in 25 mL of DMF. The mixture was de-gassed and heated at 90 C. for 4 h. Reaction mixture was concentrated and purified by chromatography (silica gel, 5% EtOAc in hexane) to give 1.8 g of the benzonitrile. MS: 316.0, 317.9 (M+1)+. The benzonitrile (1.4 g, 4.4 mmol) was dissolved in 15 mL of DMF. The reaction mixture was cooled at 0 C. Potassium carbonate (0.20 g, 1.45 mmol) was added, followed by dropwise addition of 30% hydrogen peroxide solution (1.2 mL). The cooling bath was removed and the mixture was stirred at rt for 12 h. The reaction was quenched with aqueous NaHSO3 and water. The formed precipitate was filtered and dried to give 1.1 g of the desired amide. MS: 334.2, 336.3 (M+1)+. A mixture of the resulting amide (0.2 g, 0.6 mmole), bis(pinacolato)diboron (0.228 g, 0.9 mmol) and anhydrous KOAc (0.18 g, 1.8 mmol) in 2 mL of 1,4-dioxane was purged with argon, then (1,1′)-bis(diphenylphosphino)ferrocene)palladium(II) chloride (20 mg, 0.024 mmol) was added. The resulting mixture was heated in a sealed tube in a microwave reactor at 100 C. for 2 h then left standing overnight at rt. The reaction was diluted with water and extracted 3× with EtOAc. The combined extracts were washed with brine, dried over Na2SO4, filtered and evaporated in vacuo. Chromatography on silica gel (hexane/ethyl acetate 1:1) provided the boronate (0.13 g, 57%). A mixture of this compound, the compound of Part B (0.1 g, 0.25 mmol), and K3PO4 (0.11 g, 0.5 mmol) in 5 mL dioxane was degassed and then treated with tetrakis(triphenylphosphine)palladium(20 mg, 0.017 mmol). The resulting mixture was heated in a 95-100 C. oil bath under N2 for 2 h, then stirred at rt overnight. The reaction mixture was diluted with brine and extracted 3× with EtOAc. The combined extracts were washed with brine then dried over anhydrous Na2CO3, filtered and evaporated. Chromatography on silica gel (hexane/ethyl acetate 1:1) provided the product (0.12 g, 83%) as a light yellow foam. 1H NMR (400 MHz, CDCl3) delta ppm 4.07 (s, 2H) 4.90 (s, 2H) 5.23 (s, 2H) 6.91 (d, J=6.15 Hz, 2H) 7.05 (m, 3H) 7.20 (m, 6H) 7.29 (m, 5H) 7.42 (d, J=7.91 Hz, 1H) 7.51 (d, J=10.99 Hz, 2H) 7.98 (dd, J=8.13, 1.98 Hz, 1H) 8.19 (d, J=2.20 Hz, 1H). LC/MS m/z 576.16 (M+H)+.

According to the analysis of related databases, 25252-00-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Smallheer, Joanne M.; Corte, James R.; US2005/228000; (2005); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Electric Literature of 25252-00-0, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 25252-00-0 as follows.

Part C. 3′-(1-benzyl-6-cyano-1H-indol-3-ylmethyl)-4-carbamoyl-biphenyl-2-carboxylic acid benzyl ester:; 2-Bromo-5-iodobenzoic acid (6.54 g, 20.0 mmol) was dissolved in DMF (70 mL). Potassium bicarbonate (2.2 g, 22.0 mmol) was added, followed by benzyl bromide (2.8 mL, 22.0 mmol). The mixture was stirred at rt under N2 for 12 h. The reaction mixture was poured into water and extracted with EtOAc. The combined organic solution was washed with brine, dried over MgSO4, and concentrated and dried to give 9.05 g of the benzyl ester. The ester (2.3 g, 7.69 mmol), Zn(CN)2 (1.3 g, 11.5 mmol), and Pd[PPh3]4 were dissolved together in 25 mL of DMF. The mixture was de-gassed and heated at 90 C. for 4 h. Reaction mixture was concentrated and purified by chromatography (silica gel, 5% EtOAc in hexane) to give 1.8 g of the benzonitrile. MS: 316.0, 317.9 (M+1)+. The benzonitrile (1.4 g, 4.4 mmol) was dissolved in 15 mL of DMF. The reaction mixture was cooled at 0 C. Potassium carbonate (0.20 g, 1.45 mmol) was added, followed by dropwise addition of 30% hydrogen peroxide solution (1.2 mL). The cooling bath was removed and the mixture was stirred at rt for 12 h. The reaction was quenched with aqueous NaHSO3 and water. The formed precipitate was filtered and dried to give 1.1 g of the desired amide. MS: 334.2, 336.3 (M+1)+. A mixture of the resulting amide (0.2 g, 0.6 mmole), bis(pinacolato)diboron (0.228 g, 0.9 mmol) and anhydrous KOAc (0.18 g, 1.8 mmol) in 2 mL of 1,4-dioxane was purged with argon, then (1,1′)-bis(diphenylphosphino)ferrocene)palladium(II) chloride (20 mg, 0.024 mmol) was added. The resulting mixture was heated in a sealed tube in a microwave reactor at 100 C. for 2 h then left standing overnight at rt. The reaction was diluted with water and extracted 3× with EtOAc. The combined extracts were washed with brine, dried over Na2SO4, filtered and evaporated in vacuo. Chromatography on silica gel (hexane/ethyl acetate 1:1) provided the boronate (0.13 g, 57%). A mixture of this compound, the compound of Part B (0.1 g, 0.25 mmol), and K3PO4 (0.11 g, 0.5 mmol) in 5 mL dioxane was degassed and then treated with tetrakis(triphenylphosphine)palladium(20 mg, 0.017 mmol). The resulting mixture was heated in a 95-100 C. oil bath under N2 for 2 h, then stirred at rt overnight. The reaction mixture was diluted with brine and extracted 3× with EtOAc. The combined extracts were washed with brine then dried over anhydrous Na2CO3, filtered and evaporated. Chromatography on silica gel (hexane/ethyl acetate 1:1) provided the product (0.12 g, 83%) as a light yellow foam. 1H NMR (400 MHz, CDCl3) delta ppm 4.07 (s, 2H) 4.90 (s, 2H) 5.23 (s, 2H) 6.91 (d, J=6.15 Hz, 2H) 7.05 (m, 3H) 7.20 (m, 6H) 7.29 (m, 5H) 7.42 (d, J=7.91 Hz, 1H) 7.51 (d, J=10.99 Hz, 2H) 7.98 (dd, J=8.13, 1.98 Hz, 1H) 8.19 (d, J=2.20 Hz, 1H). LC/MS m/z 576.16 (M+H)+.

According to the analysis of related databases, 25252-00-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Smallheer, Joanne M.; Corte, James R.; US2005/228000; (2005); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Application of 25252-00-0, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 25252-00-0 as follows.

Oxalyl chloride (13.0 mL) is added to an ice-cold solution of 2-bromo-5-iodo-benzoic acid (49.5 g) in CH2Cl2 (200 mL). DMF (0.2 mL) is added and the solution is stirred at room temperature for 6 h. Then, the solution is concentrated under reduced pressure and the residue is dissolved in THF (100 mL). The resulting solution is cooled in an ice-bath and LiBH4 (3.4 g) is added in portions. The cooling bath is removed and the mixture is stirred at room temperature for 1 h. The reaction mixture is diluted with THF and treated with 0.1 M hydrochloric acid. Then, the organic layer is separated and the aqueous layer is extracted with ethyl acetate. The combined organic layers are dried (Na2SO4) and the solvent is evaporated under reduced pressure to give the crude product. Yield: 47.0 g (99% of theory)

According to the analysis of related databases, 25252-00-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Boehringer Ingelheim Vetmedica GmbH; KLEY, Saskia; REICHE, Dania Birte; (42 pag.)EP3096765; (2018); B1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com

Electric Literature of 25252-00-0,Some common heterocyclic compound, 25252-00-0, name is 2-Bromo-5-iodobenzoic acid, molecular formula is C7H4BrIO2, 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.

Oxalyl chloride (13.0 mL) is added to an ice-cold solution of 2-bromo-5-iodo-benzoic acid (49.5 g) in CH2Cl2 (200 mL). DMF (0.2 mL) is added and the solution is stirred at room temperature for 6 h. Then, the solution is concentrated under reduced pressure and the residue is dissolved in THF (100 mL). The resulting solution is cooled in an ice-bath and LiBH4 (3.4 g) is added in portions. The cooling bath is removed and the mixture is stirred at room temperature for 1 h. The reaction mixture is diluted with THF and treated with 0.1M hydrochloric acid. Then, the organic layer is separated and the aqueous layer is extracted with ethyl acetate. The combined organic layers are dried (Na2SO4) and the solvent is evaporated under reduced pressure to give the crude product. [0074] Yield: 47.0 g (99% of theory)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Bromo-5-iodobenzoic acid, its application will become more common.

Reference:
Patent; Boehringer Ingelheim Vetmedica GmbH; ECKHARDT, Matthias; BUTZ, Tanja; HIMMELSBACH, Frank; MARTIN, Hans-Juergen; US2014/31540; (2014); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com