Month: July 2021

Application of 26487-67-2, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 26487-67-2 name is 1-(2-Chloroethyl)azepane hydrochloride, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

EXAMPLE 12 11-Cyano-11-[2(hexamethyleneimino)ethyl]-6,11-dihydrodibenz[b,e]oxepin oxalate To a solution of 11-cyano-6,11-dihydrodibenz[b,e]oxepin of Example 1A (7.2 g; 0.032 mole) in dry DMF (110 ml) at 5° C. is added sodium hydride (1.9 g; 0.08 mole) portionwise under a nitrogen atmosphere. After stirring at ambient temperature for 11/2 hours, the reaction is cooled to 10° C. and 2-(hexamethylene-imino)ethyl chloride hydrochloride (6.9 g; 0.035 mole) is added portionwise. Stirring is continued at 100° C. for 21/2 hours. The reaction is cooled and poured into two liters of ice water, extracted with ether and the ether back extracted with 2 N HCl. The acidic extracts are combined and made basic with sodium hydroxide. After extracting with ether, washing with a saturated NaCl solution and drying (K2 CO3), the ether is removed in vacuo to provide 3.0 g of an oil (27percent).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-(2-Chloroethyl)azepane hydrochloride, and friends who are interested can also refer to it.

Reference:
Patent; Hoechst-Roussel Pharmaceuticals Inc.; US4335122; (1982); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 4863-91-6,Some common heterocyclic compound, 4863-91-6, name is 3-Chloro-5-fluoroaniline, molecular formula is C6H5ClFN, 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.

a) 4-Bromo-3-chloro-5-fluoroaniline 3-Chloro-5-fluoroaniline (2061 mmol, 300 g) was dissolved in ACN (3000 ml) and the solution cooled to 0 C. NBS (2061 mmol, 367 g) was added to the reaction mixture in small portions keeping the temperature below 10 C. Reaction mixture was stirred at 10+-5 C. for 3.5 h. 10% Aqueous NaHSO3 was added and the reaction mixture was concentrated under vacuum to remove organic solvents. Water and DCM was added, stirred for 15 min and the phases were separated. The water phase was extracted with DCM. The combined organics were washed with water. The organic phase was evaporated. 2-Propanol was added to the residue and distilled until the steam temperature was 80 C. Water was added and the temperature was kept at 40+-10 C. The mixture was cooled to 5 C. and stirred for 4 h. The precipitate was removed by filtration, washed with water and dried under vacuum. 440.7 g of the title compound was obtained. 1H-NMR (400 MHz, DMSO-d6): delta 5.87 (s, 2H), 6.42-6.49 (m, 1H), 6.62-6.66 (m, 1H).

The synthetic route of 4863-91-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ORION CORPORATION; Toermakaengas, Olli; Wohlfahrt, Gerd; Salo, Harri; Ramasurbamanian, Rathna Durga; Patra, Pranab Kumar; Martin, Arputharaj Ebenezer; Heikkinen, Terhi; Vesalainen, Anniina; Moilanen, Anu; Karjalainen, Arja; US2014/94474; (2014); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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 210532-25-5 as follows. name: 3,5-Difluorobenzene-1-sulfonyl chloride

A solution of 3-(2-chloro-10H-phenothiazin-10-yl)propan-1-amine hydrochloride (0.080 g, 0.244 mmol) in DMF (1.5 ml) was cooled to 0 C, treated with triethylamine (71.0 muL, 0.513 mmol), and 3,5-difluorobenzenesulfonyl chloride (0.057 g, 0.268 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was poured over saturated aqueous NaCl (50 mL), and extracted with ethyl acetate (3 50 mL). The combined organic extracts were washed with saturated aqueous NaCl (2 50 mL), dried (Na2SO4), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2Cl2 and purified by flash chromatography (SiO2, 0-35% ethyl acetate-hexanes) to afford the title compound as a white solid triturated from ethyl ether-hexanes (0.0736 g, 65%). 1H NMR (600 MHz, CDCl3) 7.17-7.22 (4H, m), 7.11 (1H, d, J = 8.2 Hz), 7.01 (1H, t, J = 7.6 Hz), 6.95 (2H, m), 6.85 (1H, d, J = 8.1 Hz), 6.81 (1H, s), 5.23 (1H, t, J = 5.9 Hz), 3.93 (2H, t, J = 5.8 Hz), 3.13 (2H, dd, J = 12.2, 6.1 Hz), 1.97 (2H, quintet, J = 5.9 Hz); 13C NMR (150 MHz, CDCl3) 163.7 (d, J = 48.0 Hz), 162.0 (d, J = 44.2 Hz), 146.5, 144.5, 143.4 (t, J = 34.3 Hz), 133.8, 128.6, 128.2, 127.9, 126.0, 124.8, 123.9, 123.3, 116.3 (d, J = 52.7 Hz), 110.6 (dd, J = 85.3, 26.0 Hz), 108.3 (t, J = 100.6 Hz), 45.3, 42.0, 26.3; LCMS m/z 467.1 ([M + H+], C21H17ClF2N2O2S2 requires 467.0).

According to the analysis of related databases, 210532-25-5, the application of this compound in the production field has become more and more popular.

Reference:
Article; Kastrinsky, David B.; Sangodkar, Jaya; Zaware, Nilesh; Izadmehr, Sudeh; Dhawan, Neil S.; Narla, Goutham; Ohlmeyer, Michael; Bioorganic and Medicinal Chemistry; vol. 23; 19; (2015); p. 6528 – 6534;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 1996-29-8, 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. 1996-29-8, name is 1-Bromo-4-chloro-2-fluorobenzene belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

N. 2-CHLORO-5-CYCLOPROPYL-6-FLUOROANILINE The preparation is an adaptation of a method described in Tetrahedron Lett, Vol. 37, p. 6551 (1996). A solution of lithium DIIOSOPROPYL amide is generated by adding n-BuLi (360 mL of 2 M solution in THF) to diisopropylamine (73 g, 0.722 mol) in 500 mL of anhydrous THF while a reaction temperature OF-60C is maintained by cooling in dry-ice acetone bath. After stirring for 30 minutes, 1-bromo-4-chloro-2-fluorobenzene (75 g, 0.36 mol) is added and stirring maintained AT-70C for 2 hours. The cold solution is then transferred, via a canula, under an inert atmosphere to a suspension of solid C02 (100 g, excess) in anhydrous ET2O. The mixture is allowed to warm to room temperature with stirring and then the solvent removed by rotary evaporator. The residual solid is treated with 1 N HCI solution until PH = 3.0 and the mixture is filtered. The white solid that is obtained is suspended in 1000 mL of 2 N HCI solution and stirred for an additional 1 hour. The suspension is filtered to collect a white solid which is air dried, suspended in 100 mL of hexanes and collected to give 2-CHLORO-5-BROMO-6-FLUOROBENZOIC acid. 2-Chloro-5-bromo-6-fluorobenzoic acid (91 g, 0.36 mol) is suspended in CH2CI2 (200 mL) and treated with oxalyl chloride (51 g, 0.40 mol) by dropwise addition, immediately followed by the addition of several drops (0.1 mL) of DMF. The mixture is stirred at room temperature for 3 hours during which time the solid completely dissolves and a clear solution is obtained. The solvent is removed by rotary evaporator and the residue is added to 1000 mL of ammonium hydroxide while stirring at 0C. The product is collected by filtration and washed with water to give 2-chloro-5-bromo-6-fluorobenzamide as a white solid. A solution of sodium methoxide is generated by treating metallic sodium (18 g, 0.78 mol) with 1000 mL of anhydrous methanol by dropwise addition under an inert atmosphere. After the metal is completely consumed the solution is heated at reflux temperature for 30 minutes and then cooled to room temperature. 2-Chloro-5-bromo-6-fluorobenzamide (65 g, 0.26 mol) is added and stirring continued for an additional 30 minutes at room temperature. N-BROMOSUCCINIMIDE (92 g, 0.52 mol) is then slowly added via a powder addition funnel. The reaction mixture is warmed to 60C for 30 minutes during which time foaming is observed. The reaction mixture is cooled to room temperature and most of the solvent is removed by rotary evaporator. The residue is partitioned between EtOAc (1000 mL) and water (1000 mL). The organic layer is separated and washed with water (5 x 500 mL) and then brine (2 x 500 mL). The organic layer is dried (MGS04), filtered and concentrated by rotary evaporator to GIVE N- (2-CHLORO-5-BROMO-6-FLUOROPHENYL)-CARBAMIC acid methyl ester as a light yellow solid (m. p. 107-112C). N-(2-chloro-5-bromo-6-fluorophenyl)-carbamic ester methyl ester (8.65 g, 30.6 MMOL), cyclopropylboronic acid (3.16 g, 36.7 MMOL), potassium phosphate (22.8 g, 107 MMOL), palladium acetate (343 mg, 1.53 MMOL) and tricyclohexylphosphine (858 mg, 3.06 MMOL) are combined and stirred in a two-phase solution comprised of toluene (350 mL) and water (75 mL). The mixture is degassed by repeated alternating application of vacuum and positive nitrogen pressure (10 x). The mixture is heated to 95C for 4 days and then cooled to room temperature. The reaction mixture is partitioned between EtOAc (500 mL) and water (500 mL). The organic phase is washed with water (2 x 250 mL), brine (500 mL) and then dried (MGS04) and concentrated by rotary evaporator. The crude product is purified using flash chromatography (7-14% EtOAc/hexanes). After evaporation of the appropriate fractions the product is further purified by treating a solution in ET20 (100 mL) with charcoal, followed by filtration through Celite and evaporation. N- (2-chloro-5- cyclopropyl-6-fluorophenyl)-carbamic acid methyl ester is obtained as a white crystalline solid (m. p. 100-102C). N-(2-CHLORO-5-CYCLOPROPYL-6-FLUOROPHENYL)-CARBAMIC acid methyl ester (2.3 g, 9.4 MMOL) is dissolved in MeOH (50 mL), water (50 mL) and 30% NAOH solution (50 mL). The reaction mixture is heated to reflux temperature for 3 days and then cooled to room temperature. The reaction is concentrated by rotary evaporator to remove most of the methanol and then partitioned between ET20 (250 mL) and water (250 mL). The aqueous phase is extracted again with ET20 (150 mL) and the-combined organic layers washed with brine (250 mL), dried and concentrated by rotary evaporator. The crude product is purified by bulb-to-bulb distillation. 2-Chloro-5-cyclopropyl-6-fluoroaniline is isolated as a colorless oil (b. p. 120-135C at-20 mm of Hg).

The synthetic route of 1-Bromo-4-chloro-2-fluorobenzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2004/48314; (2004); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Related Products of 118-69-4, The chemical industry reduces the impact on the environment during synthesis 118-69-4, name is 2,6-Dichlorotoluene, I believe this compound will play a more active role in future production and life.

To a mixed solution of compound 39-a-1 (5 g, 31.06 mmol), iron powder (87 mg, 1.55 mmol) and iodine (39mg, 0.15 mmol) in carbon tetrachloride was added dropwise bromine (5.22 g, 32.61 mmol) at room temperature. Afterthe addition was complete, the reaction solution was stirred at room temperature for two days. The reaction solutionwas quenched with sodium bisulfite solution, extracted with dichloromethane (2*50 ml), and the organic phase waswashed with saturated brine (30 ml), concentrated and dried to give compound 39-a (4.77 g) as a colorless oil directlyused in the next reaction, purity 76%, yield 64%, MS m/z(ESI):N/A.

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, 2,6-Dichlorotoluene, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Shanghai Haiyan Pharmaceutical Technology Co., Ltd.; Yangtze River Pharmaceutical Group Co., Ltd.; LAN, Jiong; ZHOU, Fusheng; ZHAO, Jinzhu; HUANG, Dong; XIE, Jing; HU, Yi; LV, Qiang; (63 pag.)EP3412653; (2018); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 51572-93-1,Some common heterocyclic compound, 51572-93-1, name is O-(2,4-Dichlorobenzyl)hydroxylamine hydrochloride, molecular formula is C7H8Cl3NO, 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.

General procedure: To a solution of 3ae3e (1 mmol) in anhydrous ethanol (10 mL),corresponding O-benzylhydroxylamine hydrochloride (1 mmol)and NaOAc (1.2 mmol) were added and the resulting solution wasstirred at the room temperate for 3 h. The mixture was concentratedand taken in ethyl acetate (20 mL), washed with water(20 mL), saturated sodium chloride solution (20 mL) and dried oversodium sulfate. The resulting solution was concentrated and thepurification of the residue by recrystallization from ethanol yieldedthe desired compounds 4a-4t

The synthetic route of 51572-93-1 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Lv, Xian-Hai; Li, Qing-Shan; Ren, Zi-Li; Chu, Ming-Jie; Sun, Jian; Zhang, Xin; Xing, Man; Zhu, Hai-Liang; Cao, Hai-Qun; European Journal of Medicinal Chemistry; vol. 108; (2016); p. 586 – 593;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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. 104-52-9, name is 3-Phenylpropyl Chloride, This compound has unique chemical properties. The synthetic route is as follows., Safety of 3-Phenylpropyl Chloride

6-amino-1-ethylbenzo[cd]indol-2(1H)-one can refer to Example 1. A reaction mixture of 6-amino-1-ethylbenzo[cd]indol-2(1H)-one (100 mg, 0.47 mmol) and (3-chloropropyl)benzene (73 mg, 0.47 mmol) in CH3CN (20 mL) was stirred at rt. K2CO3 (195 mg, 1.41 mmol) was added to the reaction mixture, and stirred at 70 C. for overnight. The reaction mixture was extracted with ethyl acetate (150 mL*2). The organic layer was washed with brine and dried over Na2SO4. The solid was filtered off, and the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel chromatography with petroleum ether/ethyl acetate (5/1, v/v) to yield 1-ethyl-6-((3-phenylpropyl)amino)benzo[cd]indol-2(1H)-one (60 mg, 38%) as a yellow solid. 1H NMR (400 MHz, CDCl3) delta 8.06 (d, J=7.2 Hz, 11H), 7.84 (d, J=8.0 Hz, 1H), 7.63 (t, J=7.6 Hz, 1H), 7.32 (t, J=7.6 Hz, 2H), 7.26-7.04 (m, 3H), 6.77 (d, J=7.6 Hz, 1H), 6.34 (d, J=7.2 Hz, 1H), 4.24 (s, 1H), 3.94 (q, J=7.2 Hz, 2H), 3.30 (t, J=6.8 Hz, 2H), 2.83 (t, J=7.2 Hz, 2H), 2.21-2.03 (m, 2H), 1.36 (t, J=7.2 Hz, 3H).

According to the analysis of related databases, 104-52-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Guangzhou Institutes of Biomediciene and Health, Chinese Academy of Sciences; XU, Yong; XUE, Xiaoqian; ZHANG, Yan; SONG, Ming; (42 pag.)US2018/8574; (2018); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 3972-56-3, These common heterocyclic compound, 3972-56-3, name is 1-tert-Butyl-4-chlorobenzene, 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.

100 ml of 60% nitric acid was added dropwise to 100 ml of 95% sulfuric acid at a temperature of 35C or less, under ice-cooling, to prepare a mixed acid solution. 100 g (0.593 mol) of 4-tert-butylchlorobenzene (A-1) was added dropwise to this mixed acid solution, at a temperature of 30C or less, followed by after-reaction (20 to 25C) for 2.5 hours. The reaction solution was poured into cold water, and it was then extracted with 100 ml of toluene, followed by washing with water, to obtain a toluene solution of (A-2).

The synthetic route of 3972-56-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; FUJI PHOTO FILM CO., LTD.; EP1535898; (2005); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Electric Literature of 2687-12-9, A common heterocyclic compound, 2687-12-9, name is Cinnamyl chloride, molecular formula is C9H9Cl, 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 1Obtaining 2- (3-N,N-diisopropylamine-l-phenylpropyl) -A- carboxyphenol (IVa)(IVa) Diisopropylamine (2.77 1, 19.65 mol) and sodium iodide(16.95 g, 0.13 mol) were loaded onto a solution of cinnamyl chloride (1 kg, 6.55 mol) in ethanol (3 I/kg) at 20/250C. The mixture was heated at internal 80-850C, the reaction conditions being maintained for 3-4 hours until the end of such reaction.The mixture was cooled at 40-450C and distilled to an internal volume of 1.3 1. The mixture was then cooled at 20- 25C, water (4 1) and toluene (3 1) was added and the pH was adjusted to 1.0-1.5. The phases were decanted and dichloromethane (4 1) was loaded onto the aqueous phase, adjusting the pH again to 11.5-12.0. The phases were decanted and the organic phase was washed with water (4 1) . Once the phases were decanted, the organic phase was distilled at atmospheric pressure to an internal volume of 1.3 1 in order to then load heptane (0.5 1) . Again, it was distilled to 1.3 1 and heptane (2 1) was loaded.The suspension which was obtained was filtered by a prelayer, which was washed with heptane (0.5 1) . The filtered organic phase was distilled at atmospheric pressure to an internal volume of 1.3 1.The amine content of the reaction mixture was determined by the potentiometric titration thereof.

The synthetic route of 2687-12-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; RAGACTIVES, S.L.U.; LORENTE BONDE-LARSEN, Antonio; MARTIN PASCUAL, Pablo; LADERAS MUNOZ, Mario; GUTIERREZ FUENTES, Luis Gerardo; WO2011/12584; (2011); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 2106-02-7,Some common heterocyclic compound, 2106-02-7, name is 2-Chloro-4-fluoroaniline, molecular formula is C6H5ClFN, 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.

A mixture of (S)-1-(1-(3-chlorophenyl)-2-hydroxyethyl)-3-(1-(2-chloropyrimidin-4-yl)-1H-pyrazol-4-yl)urea (0.02 g, 0.05 mmol), 2-chloro-4-fluoroaniline (0.009 g, 0.6 mmol), potassium carbonate (0.01 g, 0.075 mmol), and dioxane (2 mL) in a glass tube was purged with nitrogen gas for 20 min. Tris(dibenzylideneacetone)dipalladium(0) (0.002 g, 0.0025 mmol) and BINAP (0.003 g, 0.005 mmol) were added to the reaction mixture, which was purged with nitrogen gas for another 15 min. The tube was sealed and heated at 90 C. for 4 hours. Reaction mixture was filtered through Celite, and filtrate was evaporated; residue was suspended in water, and extracted with ethyl acetate. Organic layer was dried over sodium sulfate, evaporated, and the residue was purified by column chromatography over silica gel using 60% ethyl acetate in hexanes as eluent to give (S)-1-(1-(2-((2-chloro-4-fluorophenyl)amino)pyrimidin-4-yl)-1H-pyrazol-4-yl)-3-(1-(3-chlorophenyl)-2-hydroxyethyl)urea (0.003 g, 12%). 1HNMR (400 MHz, CDCl3, plus a few drops MeOD): 8.50 (s, 1H), 8.33 (d, J=5.2 Hz, 1H), 8.27-8.25 (m, 1H), 7.51 (s, 1H), 7.28-7.19 (m, 1H), 7.23-7.12 (m, 3H), 7.12-7.10 (m, 1H) 7.04-6.99 (m, 1H), 6.23 (d, J=6.8 Hz, 1H) 4.87-4.84 (m, 1H), 3.81-3.77 (m, 1H), 3.64-3.61 (m, 1H). LC-MS calcd exact mass 501.09, found m/z 502.3 [M+H]+. HPLC purity 98.17%.

The synthetic route of 2106-02-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Asana Biosciences, LLC; Venkatesan, Aranapakam M.; Thompson, Scott K.; Smith, Roger A.; Reddy, Sanjeeva P.; (166 pag.)US2016/362407; (2016); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics