Month: September 2021

Reference of 328-84-7, 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. 328-84-7, name is 3,4-Dichlorobenzotrifluoride belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

a. 1,3-Bis(2-chloro-alpha,alpha,alpha-trifluoro-p-tolyloxy)benzene A solution of potassium hydroxide (3.26 g. 0.05 mole, 85%) in water (~3 g.) is added slowly dropwise to a solution of resorcinol (2.75 g. 0.025 mole) and 3,4-dichloro-alpha,alpha,alpha-trifluorotoluene (10.75 g. 0.05 mole) in sulfolane (125 ml) at 150-160 C., with stirring. When the addition is complete, the strongly colored reaction mixture is stirred at 150-160 C. overnight, then cooled, diluted with benzene (200 ml), and washed cautiously with water (700 ml). Hexane (200 ml) is added and the mixture washed with water (600 ml), dilute sulfuric acid (600 ml), dilute sodium hydroxide solution (600 ml), and water (600 ml), dried, and the solvent removed to give 1,3-bis(2-chloro-alpha,alpha,alpha-trifluoro-p-tolyloxy)benzene (8.6 g. 65%) b.p. 160-70 C./0.1 mm.

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

Reference:
Patent; Rohm and Haas Company; US31455; (1983); E1;; ; Patent; Rohm and Haas Company; US4063929; (1977); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 38762-41-3, 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 38762-41-3 as follows.

To a solution of 4-bromo-2-chloro-phenylamine (32 g, 0.15 mol) and pyridine (13.45 g, 0.17 mol) in DCM (200 mL) was added 3-chloropropionyl chloride (21.65 g, 0.17 mol) dropwise at 15 C. After stirring at room temperature for 1 hour, the mixture was washed with water and then aqueous 2N HC1. The organic layer was dried over anhy. Na2S04, filtered, and concentrated in vacuo to afford title compound (10.9 g, 90%) as a white solid.

According to the analysis of related databases, 38762-41-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; AEBI, Johannes; AMREIN, Kurt; HORNSPERGER, Benoit; KUHN, Bernd; MAERKI, Hans P.; MARTIN, Rainer E.; MAYWEG, Alexander V.; TAN, Xuefei; (77 pag.)WO2016/66597; (2016); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 38762-41-3, 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. 38762-41-3 name is 4-Bromo-2-chloroaniline, 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.

Synthesis of methyl 4?-amino-3 ?-chlorobiphenyl-4-carboxylate (65): A mixture of 4-bromo-2-chloroaniline (10 g, 48.5 mmol), 4-(methoxycarbonyl)phenylboronic acid (9.6 g,53.4 mmol), Pd(dppf)C12 (3.6 g, 4.85 mmol) and K2C03 (13.4 g, 97 mmol) in dioxane (100 mL) and water (10 mL) was degassed and heated at 100C for 2 h. After cooling down to room temperature, the reaction mixture was poured into water, extracted with EtOAc (100 mL X 3). The combined organic solvents were dried over anhydrous Na2504, concentrated under reduced pressure and purified by silica gel chromatography (10-50% EtOAc/petroleum ether) to give 11 g of methyl 4?-amino-3?-chlorobiphenyl-4-carboxylate 65 as black solid (86% yield). LCMS: m/z 262.1 [M+H], , tR= 1.98 min

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Bromo-2-chloroaniline, and friends who are interested can also refer to it.

Reference:
Patent; KARYOPHARM THERAPEUTICS INC.; BALOGLU, Erkan; SHACHAM, Sharon; SENAPEDIS, William; (153 pag.)WO2017/31213; (2017); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 6223-78-5, name is 2,5-Dichloro-2,5-dimethylhexane, A new synthetic method of this compound is introduced below., SDS of cas: 6223-78-5

To 2,5-dimethyl-2,5-hexanediol (10 g, 68.5 mmol) in a 500 mL flask was added reagent grade concentrated HCl (150 mL) and the solution was stirred at ambient temperature for 1 h. Water (100 mL) and CH2Cl2 (100 mL) were then added slowly and the layers were separated. The aqueous layer was washed with additional CH2Cl2 (100 mL). The combined organic layers were dried over MgSO4 and filtered thru silica gel pad. The solvent was removed to yield 10.9g (87%) of 2,5-dichloro-2,5-dimethylhexane. The dichloride was dissolved in 150 mL Of CH2Cl2 and 9.6 mL of toluene (90 mmol) was added. AlCl3 (390 mg, 2.9 mol) was added in portions over 5 min at ambient temperature. HCl is evolved and the solution turns dark red. The reaction was placed in an ice-bath and quenched with deionized water (120 mL). Hexane (150 mL) was added and the organic layer was removed. The aqueous layer was washed with additional hexane (150 mL). The combined organic layers were washed with water (200 mL) and brine (100 mL) and dried over MgSO4. The solvent was removed in vacuo to give l,l,4,4,6-pentamethyl-l,2,3,4- tetrahydronaphthalene as a colorless oil that crystallized after storage at -2O0C.[0155] Yield: 12 g (91%); low melting white solid; Rf = 0.7 in 100% hexane.[0156] 1H-NMR (CDCl3, 300 MHz) delta 1.32 (s, 12H), 1.7 (s, 4H), 2.34 (s, 3H), 6.85 (dd, IH), 7.14 (d, IH), 7.22 (d, IH)[0157] 13C-NMR (CDCl3, 75 MHz) delta 21.54, 32.26, 32.32, 34.29, 34.51, 35.57, 35.63, 126.64, 126.75, 127.21, 134.93, 142.00, 144.83.

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; AUSPEX PHARMACEUTICALS, INC.; WO2007/22437; (2007); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

19752-55-7, name is 1-Bromo-3,5-dichlorobenzene, belongs to chlorides-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. SDS of cas: 19752-55-7

Magnesium turning (2.8 g) and iodine (50 mg) were added to a 250 mL three-necked round bottom flask and stirred under an argon atmosphere for 30 minutes. 1-bromo-3,5-dichlorobenzene (20.7 g) dissolved in tetrahydrofuran was slowly added dropwise, heated to reflux for 2 hours, and then cooled to room temperature. In another round bottom flask, trimethoxyboraine (33.8 mL) was dissolved in 80 mL of diethyl ether. After cooling to -15 C, a previously prepared Grignard reagent was added dropwise through a cannula. Slowly raised to room temperature and stirred for 12 hours. The resulting white solid was washed with pentane and the filtrate was concentrated under reduced pressure to give 14.6 g of the title compound.

The synthetic route of 19752-55-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Dae Joo Electronic Materials Co., Ltd.; Jeon Yeong-min; Park Jeong-gyu; Lee Hyeon-seok; Kim Min-yeong; (50 pag.)KR2019/106313; (2019); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 831-81-2, A common heterocyclic compound, 831-81-2, name is 4-Chlorodiphenylmethane, molecular formula is C13H11Cl, 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.

General procedure: In around-bottom flask, diarylmethanes (1.0 mmol), NBS (889.9 mg, 5.0 mmol) andwater (0 or 5.0 mmol) were dissolved in CHCl3 (4.0 mL). After refluxingfor 3 h in the air, the reaction mixture was quenched withNa2S2O3·5H2O, cooled to roomtemperature, washed with 5mL CH2Cl2, dried with MgSO4,and filtered to get clear organic solution. The solvent was removed reducedpressure by a rotary evaporator, and the resulting residue was subjected tocolumn chromatography on silica gel using co-solvent(ethyl acetate / petroleum ether, v/v) as eluent to give the correspondingdiaryllketones.

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Article; He, Chao; Zhang, Xiaohui; Huang, Ruofeng; Pan, Jing; Li, Jiaqiang; Ling, Xuege; Xiong, Yan; Zhu, Xiangming; Tetrahedron Letters; vol. 55; 32; (2014); p. 4458 – 4462;,
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 63624-28-2 as follows. Product Details of 63624-28-2

Example 199; 1 -(2,4-Dimethoxybenzensulfonyl)-2-oxo-3-{2-oxo-1 -phenyl-2-[(S)-3-(4- propylpiperazin-1 -yl)pyrrolidin-1 -yl]ethyl}-2,3-dihydro-1 H-benzimidazole-5- carbonitrile; To a solution of 2-oxo-3-{2-oxo-1-phenyl-2-[(S)-3-(4-propyl-piperazin-1-yl)-pyrrolidin- 1-yl]-ethyl}-2,3-dihydro-1 H-benzoimidazole-5-carbonitrile (32 mg, 0.07 mmol), triethylamine (0.02 ml_, 0.13 mmol) and DMAP (catalytic amount) in CH2CI2 (2 ml.) 2,4-dimethoxybenzenesulfonyl chloride (17 mg, 0.077 mmol) was added. The reaction mixture was stirred at room temperature for 24 hours, diluted with water and extracted the aqueous phase with CH2CI2 (3 x). The combined organic phase was washed with saturated NaHCO3 aqueous solution, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography in silica gel using 4% methanol in CH2CI2 as eluent to afford 1-(2,4-dimethoxy- benzenesulfonyl)-2-oxo-3-{2-oxo-1-phenyl-2-[(S)-3-(4-propyl-piperazin-1-yl)- pyrrolidin-1-yl]ethyl}-2,3-dihydro-1 H-benzoimidazole-5-carbonitrile (29 mg, 66%) as a white solid. 1H-NMR (400 MHz, CDCI3): delta 0.88-0.94 (m, 3H), 1.28 (m, 2H), 1.84 (m, 1 H), 2.14 (m, 1 H), 2.25-2.59 (m, 9H), 2.79-3.12 (m, 2H), 3.23-3.58 (m, 2H), 3.48 (s, 3H), 3.73- 3.99 (m, 2H), 3.89 (s, 3H), 6.36-6.44 (m, 2H), 6.65 (d, 8.9 Hz, 1 H), 7.00-7.10 (m, 1 H), 7.22-7.26 (m, 2H), 7.34-7.39 (m, 4H), 7.94 (d, 8.5 Hz, 1 H), 8.14 (d, 8.9 Hz, 1 H). MS (API-ES, pos) m/z = 673

According to the analysis of related databases, 63624-28-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ABBOTT GMBH & CO. KG; WO2008/25736; (2008); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 2106-04-9,Some common heterocyclic compound, 2106-04-9, name is 3-Chloro-2-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.

Example 1 (4S)-4- ({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)-N- cyclopropyl-1-methyl-D-prolinamide Example 1 HATU (0.23g) was added to an agitated solution of (4Y)-4- ( {4- [ (3-CHLORO-2- fluorophenyl) AMINO]-7-METHOXYQUINAZOLIN-6-YL} OXY)-1-METHYL-D-PROLINE (7) (0.18g), cyclopropylamine (34.4mg) and DIPEA (156mg) IN METHYLENE CHLORIDE (5M1). After 16hrs the reaction mixture was reduced in vacuo. The residues were re-dissolved in methylene chloride and washed with sodium hydroxide solution (2M) and water. The organic phase was then purified by column chromatography on silica eluting with increasingly polar mixtures of METHANOL/METHYLENE CHLORIDE (0/100-10/90). THE fractions containing the desired product were combined and evaporated to a foam which was triturated with diethylether to give the title compound as a white solid. (0. 15G). LH NMR Spectrum : (DMSO d6) 0.40-0. 48 (m, 2H), 0.57-0. 64 (M, 2H), 2.05-2. 14 (M, 1H), 2.28 (s, 3H), 2.33-2. 45 (M, 1H), 2.48-2. 56 (M, 1H + DMSO), 2. 61-2. 70 (M, 1H), 3.08 (t, 1H), 3.64 (dd, 1H), 3.94 (s, 3H), 5.06 (M, 1H), 7.20 (s, 1H), 7.28 (t, 1H), 7.44-7. 56 (M, 2H), 7.65 (s, 1H), 7.87 (d, 1H), 8.35 (s, 1H), 9.63 (s, 1H); Mass SPECTRUM : (M+H) + 486. 44 The starting material 1, 2-PYRROLIDINEDICARBOXYLIC acid, 4-hydroxy-, 1- (1, 1-DIMETHYLETHYL) 2- methyl ester, (2R, 4R) (2) was prepared as follows: 1- [3- (DIMETHYLAMINO) PROPYL]-3-ETLIYLCARBODIIMIDE hydrochloride (14.73 g) was added to a stirred suspension of 1, 2-PYRROLIDINEDICARBOXYLIC acid, 4-hydroxy-, l- (l, l-dimethylethyl) ester, (2R, 4R) (1) (13.65 g), DIMETHYLAMINOPYRIDINE (21.65 g) and methanol (5.67 g) in methylene chloride (400 ml) and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was washed with citric acid (1.0 M), saturated aqueous sodium bicarbonate solution and saturated brine, dried over MgSO4, filtered and evaporated. The residues were then purified by column chromatography on silica eluting with increasingly polar mixtures of METHANOL/METHYLENE chloride (1/99-5/95). The desired product fractions were combined and evaporated to give 1, 2-PYNOLIDINEDICARBOXYLIC acid, 4-hydroxy-, L- (L, L-DIMETHYLETHYL) 2- methyl ester, (2R, 4R) (2) as a white crystalline solid, (5.9 g). 1H NMR Spectrum : (DMSO d6) 1.32 + 1.38 (2s, 9H), 1.76-1. 87 (M, 1H), 2.24-2. 28 (M, 1H), 3.06-3. 15 (M, 1H), 3.42- 3. 51 (m, 1H), 3.60 + 3.63 (2s, 3H), 4.15-4. 24 (M, 2H), 4.92-5. 00 (M, 1H). Starting material 1, 2-Pyrrolidinedicarboxylic acid, 4-hydroxy-1- (1, 1-dimethylethyl) ester, (2R, 4R), (1), (Boc-D-cis-hyp-OH) is commercially available Starting material (3) was prepared as follows: 6-Acetoxy-4-chloro-7-methoxyquinazoline, (Example 25-5 of in W001/66099 ; 10. 0g, 39.6 MMOLE) was added in portions to a stirred 7N methanolic ammonia solution (220 ML) cooled to 10C in an ice/water bath. After stirring for one hour the precipitate was filtered, washed with diethylether and dried thoroughly under high vacuum to give 4-chloro-7- METHOXYQUINAZOLIN-6-OL (3) (5.65g, 67.8%) ; 1H NMR Spectrum : (DMSO d6) 3.96 (s, 3H); 7.25 (s, 1H); 7.31 (s, 1H); 8.68 (s, 1H) ; Mass Spectrum: (M+H) + 211. The starting material (4) was prepared as follows: Di-ethyl azodicarboxylate (5.71g) was added slowly to a stirred suspension of 1,2- PYNOLIDINEDICARBOXYLIC acid, 4-hydroxy-, L- (L, L-DIMETHYLETHYL) 2-methyl ester, (2R, 4R) (2) (5.9g), 4-CHLORO-7-METHOXYQUINAZOLIN-6-OL (3) (4.6g) AND TRIPHENYLPHOSPHINE (8.6g) in methylene chloride (400 ML) at 25C under an atmosphere of nitrogen and the reaction mixture was stirred for 2 hours. The reaction mixture was then evaporated to ½ volume and purified by column chromatography on silica eluting with increasingly polar mixtures of METHANOL/METHYLENE chloride (1/99-3/97). The desired product fractions were combined and evaporated to give 1-tert-butyl 2-methyl (2R, 4S)-4-[(4-chloro-7-methoxyquinazolin-6- yl) oxy] pyrrolidine-1, 2-dicarboxylate (4) as a pale yellow gum. This was used in the preparation of (5) without further purification. The starting material methyl (4S)-4-({4-[(3-CHLORO-2-FLUOROPHENYL) AMINO]-7- METHOXYQUINAZOLIN-6-YL} OXY)-D-PROLINATE HYDROCHLORIDE (5) was prepared as follows: 4. 0M HCl in Dioxane (15 ml) was added to a suspension of 1-tert-butyl 2-methyl (2R, 4S)-4- [(4-chloro-7-methoxyquinazolin-6-yl0 oxy] pyrrolidine-1, 2-dicarboxylate (4) AND 3-CHLORO-2- fluoroaniline (2.89g) in acetonitrile (400 ML) and the reaction mixture was stirred and heated at 70C for 3 hours. The resulting precipitate was filtered hot and washed with acetonitrile and diethylether and dried under vacuum to give methyl (4S)-4- (14- [ (3-CLILORO-2- FLUOROPHENYL) AMINO]-7-METHOXYQUINAZOLIN-6-YL} OXY)-D-PROLINATE HYDROCHLORIDE (S) as an off- white solid, (6. 3G). TH NMR Spectrum : (DMSO D6) 2.46-2. 60 (M, 2H), 3.37-3. 46 (M, 1H), 3.71 (s, 3H), 3.89-3. 98 (m, 4H), 4.53 (t, 1H), 5.42 (M, 1H), 7.29 (t, 1H), 7.38-7. 48 (M, 2H), 7.55 (t, 1H), 8.64 (s, 1H), 8.75 (s, 1H)…

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Chloro-2-fluoroaniline, its application will become more common.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2005/30757; (2005); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 118-69-4, name is 2,6-Dichlorotoluene, belongs to chlorides-buliding-blocks compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 118-69-4, Quality Control of 2,6-Dichlorotoluene

To a 25 mL reaction flask was added 1,3-diphenylpropanedione iron (0.025 mmol) in turn,Ferrous phthalocyanine (0.0025 mmol),Triethoxy carveda (1.5 mmol)Sodium persulfate (0.75 mmol),(L · 25 mmol), acetone (lmL), water (lmL), and the reaction mixture was reacted at 80 C for 17 h. The reaction was terminated with the addition of aqueous ammonia (2 mL) to remove the polymethylhydrogensiloxane, 10 mL of saturated brine was added and extracted with ether (10 mL X3). The organic phases were combined and the solvent was evaporated under reduced pressure.To 60% yield.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; Nanjing Normal University; Han Wei; Zhao Hongyuan; (14 pag.)CN107216242; (2017); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Related Products of 452-83-5, 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. 452-83-5 name is 2-Chloro-5-fluoroaniline, 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.

General procedure: NaOt-Bu (0.240 g, 2.5 mmol), Pd(OAc)2 (0.006 g, 0.025 mmol) and [HPt-Bu3][BF4] (0.010 g, 0.035 mmol) were suspended in toluene (3 ml) in a 5 ml microwave vial. The appropriate 2-chloroaniline (0.50 mmol) and aryl bromide (0.50 mmol) were then added and the vial sealed. The reaction was then heated in the microwave reactor at 160 C for 3 h, allowed to cool, and then quenched by addition of aqueous HCl (2 M, 3 ml). The organic phase was extracted with CH2Cl2 (2×20 ml), dried (MgSO4), then filtered and the solvent removed under reduced pressure. The crude product mixture was then subjected to column chromatography (SiO2).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Chloro-5-fluoroaniline, and friends who are interested can also refer to it.

Reference:
Article; Bedford, Robin B.; Bowen, John G.; Weeks, Amanda L.; Tetrahedron; vol. 69; 22; (2013); p. 4389 – 4394;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics