Category: chlorides-buliding-blocks

A common heterocyclic compound, 2770-11-8, name is 2-(4-Chlorophenoxy)aniline, molecular formula is C12H10ClNO, 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. 2770-11-8.

2-(4-Chlorophenoxy)aniline (200 mg, 0.9107 mmol, 1.1 eq) and JV-(3-acetylphenyl)-iV- ethylacetamide (169 mg, 0.827 mmol, 1 eq) were stirred in dry dichloromethane (DCM) at room temperature for 10 min. Tri-isopropoxytitanium chloride (395 muL, 1.654 mmol, 2 eq) was added to the reaction mixture which was stirred at room temperature for 16 hours. Sodium triacetoxyborohydride (700 mg, 3.308 mmol, 4 eq) was then added to the reaction mixture and was stirred at room temperature for a further 24 h. The reaction mixture was then poured onto a solution of saturated aqueous sodium bicarbonate (100 mL) and extracted with DCM (120 mL). The organic layer was washed with brine (120 mL), dried over MgSO4, filtered and concentrated to give the crude as a yellow oil. Purification of the crude by flash chromatography (ISCO) eluting with a gradient [from 25% ethyl acetate in petrol ether to 50% ethyl acetate in petrol ether] gave (87 mg, 26 %) as a white solid. 1H NMR (270 MHz, CDCl3) delta 1.05 (3H, t, J = 8.1 Hz, CH3), 1.49 (3eta, d, J = 6.4 Hz CH3), 1.67 (3H, s, CH3), 3.68 (2H, q, J= 8.1 Hz, CH2), 4.45-4.60 (2H, m, NH and CH) 6.37 (1eta, d, J = 8.2 Hz, ArH), 6.57 (IH, dt, J = 1.4, 8.2 Hz ArH), 6.75-7.06 (6H, m, ArH), 7.23-7.39 (4H, m, ArH); 13C NMR (67.5 MHz, CDCl3) delta 13.1, 22.8, 25.0, 43.8, 52.8, 112.0, 112.9, 117.2, 118.7, 119.3, 125.0, 126.1, 126.5, 128. 0, 129.8, 130.0, 138.0, 139.1, 142.8, 147.1, 156.5, 169.9 LCMS (90% MeOH and 10% H2O; Symmetry C18 reverse phase column) tr = 2.88 min; (ES+), m/z 409.2 (35ClM’, 75%), 383 (37ClM’, 25%); HRMS (ESI) calcd. for C24H25ClN2O2 (M+H)+ 409.1605, found 409.1689. 99.48% purity.

The synthetic route of 2-(4-Chlorophenoxy)aniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; STERIX LIMITED; WO2009/66072; (2009); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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. 1193-72-2 name is 1-Bromo-2,4-dichlorobenzene, 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. 1193-72-2

Part C. tert-butyl (7bR,11aS)-6-(2,4-dichloroanilino)-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate. An oven dried three-necked round bottom flask was fitted with septa, condenser, and a stopper. The flask was charged with tert-butyl (7bR,11aS)-6-amino-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate (134 mg, 0.36 mmol), 1-bromo-2,4-dichlorobenzene (70 mg, 0.31 mmol), NaOtBu (60 mg, 0.62 mmol), and anhydrous toluene (5 mL). The solution was purged with argon at 80 C. for 25 min then cooled to room temperature. While maintaining a blanket of argon, Pd2(dba)3 (3.4 mg, 3.7 mumol), and BINAP (7 mg, 11.2 mumol) were added quickly. The resulting mixture was heated to 80 C. for 20 hours under argon while monitoring the consumption of starting material by TLC (50% ethyl acetate/hexanes). After cooling to room temperature, the dark solution was diluted with ethyl ether (10 mL) and filtered through a pad of silica, washing with ether and ethyl acetate. The resulting solution was concentrated and chromatographed (Combiflash, 95:5 to 75:25 hexanes/ethyl acetate gradient) yielding the title compound (78 mg, 48%) as a tan solid. 1H NMR (CDCl3, 300 MHz) delta 1.41 (s, 9H), 1.79-1.97 (m, 2H), 2.85-3.18 (m, 6H), 3.46-3.61 (m, 4H), 3.68 (s, 2H), 5.84 (s, 1H), 6.71 (d, 1H, J=1.9 Hz), 6.79 (d, 1H, J=1.8 Hz), 6.89 (d, 1H, J=8.8 Hz), 7.01 (dd, 1H, J=2.3, 8.8 Hz), 7.29 (d, 1H, J=2.3 Hz) ppm.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Bromo-2,4-dichlorobenzene, and friends who are interested can also refer to it.

Reference:
Patent; Robichaud, Albert J.; Fevig, John M.; Mitchell, Ian S.; Lee, Taekyu; Chen, Wenting; Cacciola, Joseph; US2004/186094; (2004); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Some common heterocyclic compound, 823-57-4, name is 2-Bromo-5-chloroaniline, molecular formula is C6H5BrClN, 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. 823-57-4

The corresponding imidazopyridine (0.2 mmol) was added sequentially to a 25 ml Schlenk tube filled with oxygen and equipped with a magnetic stirrer at room temperature.Cuprous bromide (0.02 mmol), 2-bromo-5-chloroaniline (0.4 mmol),1,10-azaphenanthroline (0.04 mmol), pyridine (0.4 mmol),Carbon disulfide (0.4 mmol), NMP (2.0 mL), was added with a syringe under oxygen.The reaction tube was placed in a 130 C oil bath for 10 hours.The resulting solution was cooled to room temperature, and 2 mL of deionized water was added to the reaction solution.Mix well, each time with 3mL of ethyl acetate as extractant through liquid separation extraction operation,The crude product is extracted from the reaction solution, and the extract is combined.And removing the solvent by a rotary evaporator;The residue was purified on a silica gel column (silica gel size 200 mesh to 300 mesh,The eluent is petroleum ether/ethyl acetate (15:1 v/v),The target product was obtained in 69.1 mg, yield 82%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 823-57-4, its application will become more common.

Reference:
Patent; Qingdao University of Science and Technology; Yang Daoshan; Yan Qiuli; (17 pag.)CN110294757; (2019); A;,
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 344-19-4 as follows. 344-19-4

Method 2: Example 27: [2-(2,6-Dichloro-4-fluorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-yl]-(6-methylpyrimidin-4-yl)amine Step 1 : l-(4-Azidopyridin-3-yl)meth-(E)-ylidene]-(2,6-dichloro-4-fluorophenyl)amine Titanium tetrachloride (1M, 4.0 mL, 4.15 mmol) was added to a cooled (0 C) mixture of 4-azidopyridine-3- carbaldehyde (1.0 g, 6.75 mmol), 2,6-dichloro-4-fluorophenylamine (1.22 g, 6.75 mmol) and triethylamine (2.8 mL, 20.3 mmol) in DCM (24 mL), under nitrogen. The reaction was stirred for 30 minutes at 0 C, warmed to room temperature, stirred for an additional 2 h, and concentrated under reduced pressure. The residue was dissolved in toluene and filtered though a pad of Celite. The filtrate was concentrated to dryness under reduced pressure to afford the title compound as a yellow solid (2.09 g, quant.). This crude material was employed in the next step without further purification or analysis.

According to the analysis of related databases, 344-19-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; BLENCH, Toby; GOODACRE, Simon; LAI, Yingjie; LIANG, Yun; MACLEOD, Calum; MAGNUSON, Steven; TSUI, Vickie; WILLIAMS, Karen; ZHANG, Birong; WO2012/66061; (2012); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

2533-69-9, These common heterocyclic compound, 2533-69-9, name is Methyl 2,2,2-trichloroacetimidate, 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.

Methyl 2,2,2-trichloroacetimidate (408 ml, 3.30 mmol), diisopropylethylamine (473 ml, 2.72 mmol) and ammonium chloride (73 mg, 1.36 mmol) were added to a solution of compound 96 (943 mg, 3.00 mmol) in acetic acid (6.0 ml) under ice-cooling, and the mixture was stirred for 45 minutes at room temperature. After water (15 ml) was added to the reaction mixture, precipitated crystals were collected and dissolved in THF (27 ml). 5 N sodium hydroxide solution (3 ml) was added to the solution and the mixture was stirred for 1 .5 hours at room temperature. The reaction mixture was concentrated and acidified to pH 3 – 4 with 2 N hydrochloric acid. Precipitated crystals were collected and washed with water to give compound 99 (770 mg, 70 %) as reddish-brown crystals. NMR (CDCl3) ?: 4.28 (3H, s), 4.45 (2H; s), 7.06 (2H, m), 7:33-(1H; d; J=8.5Hz), 7.39 (2H, m), 7.80 (1H, d, J = 8.6 Hz).

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 2533-69-9.

Reference:
Patent; SHIONOGI & CO., LTD.; EP1375486; (2004); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

363-51-9, These common heterocyclic compound, 363-51-9, name is 2-Chloro-6-fluoroaniline, 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.

Acetic anhydride (10 mL, 106 mmol) was added to a solution of 2-chloro-6-fluoroaniline (12.81 g, 88 mmol) in AcOH (44 mL) and the mixture was stirred at 90 C. for 2 hrs. After cooling to r.t., water was added and the solid precipitate was collected by filtration, washed with water, and air dried to afford N-(2-chloro-6-fluorophenyl)acetamide (16.2 g, 98% yield) as a white solid. The crude product obtained was used directly in the next step without further purification. LCMS calculated for C8H8ClFNO (M+H)+: m/z=188.0; Found 188.0.

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 363-51-9.

Reference:
Patent; Incyte Corporation; Hummel, Joshua; Vechorkin, Oleg; Sokolsky, Alexander; Ye, Qinda; Liu, Kai; Yao, Wenqing; (60 pag.)US2020/48241; (2020); A1;,
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. 1996-30-1, name is 3-Bromo-4-fluorochlorobenzene, This compound has unique chemical properties. The synthetic route is as follows., 1996-30-1

2-fluoro-5-chlorobromobenzene 18a (11.0g, 52.8mmol), ethynyltrimethyl Silane (7.7 g, 79 mmol) and triethylamine (60 mL) were mixed, and then cuprous iodide (100 mg, 0.53 mmol) and ditriphenylphosphine palladium chloride (1.86 g, 2.65 mmol) were added.The reaction mixture was heated to 80 C under a nitrogen atmosphere and stirring was continued for 4 hours.After the reaction was completed, the solution was desolvated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 100/1) to obtain the target product ((2-fluoro-5-chlorophenyl) ethynyl) trimethyl. Silane 18b (11.0 g, yellow oil), yield: 90%.

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; BEIJING TIANCHENG PHARMA CO., LTD.; CHEN, XIANGYANG; GAO, YINGXIANG; KONG, NORMAN XIANGLONG; (118 pag.)TW2019/38538; (2019); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

These common heterocyclic compound, 2613-34-5, name is 3-Chloro-2,4-difluoroaniline, 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. 2613-34-5

3-CHLORO-2, 4-DIFLUOROANILINE (1.7 g, 10.1 mmol) and 5N hydrogen chloride in isopropanol (2 ml) were added to a suspension of tert-butyl 4- [ (4-CHLORO-7-METHOXYQUINAZOLIN-6- yl) oxy] PIPERIDINE-1-CARBOXYLATE (4 g, 10.1 mmol, PCT Int. Appl. W02003082831, AstraZeneca) in isopropanol (50 ml). The mixture was stirred at 80C for 3 hours. After evaporation of the solvents, the residue was purified by chromatography on silica gel (eluant: 5-10% 7N methanolic ammonia in dichloromethane) to give 4- (3-CHLORO-2, 4-difluoroanilino) – 7-METHOXY-6-[(PIPERIDIN-4-YL) OXY] QUINAZOLINE (3.63 g, 85%) as a white solid. HNMR Spectrum: (CDC13 + CD3CO2D) : 2.15 (m, 2H), 2.30 (m, 2H), 3.34 (m, 2H), 3.47 (m, 2H), 4.01 (s, 3H), 4.91 (m, 1H), 7.03 (m, 1H), 7.58 (m, 2H), 7.90 (s, 1H), 8.55 (s, 1H) ; Mass spectrum: MH+ 421.

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 2613-34-5.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2005/28470; (2005); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

The chemical industry reduces the impact on the environment during synthesis 823-57-4, name is 2-Bromo-5-chloroaniline, I believe this compound will play a more active role in future production and life. 823-57-4

Compound 37b (4.2 g, 20.3 mmol) is melted at 500C in a 100 mL round-bottomed flask containing a stirring bar and immersed in an oil bath. A solution of zinc chloride (700 mg, 5.03 mmol) and ferric chloride (540 mg, 3.25 mmol) in 3.3 mL of water is added in one portion followed by 20 m L of absolute EtOH. The flask is stoppered with a rubber septa and a needle is inserted to avoid any pressure build-up. The mixture is warmed to 800C and acrolein (1.68 mL, 24.4 mmol) is added via a syringe pump over a 2 h period. After the addition, the mixture is stirred at 800C for 1 h and an additional amount of solid ferric chloride is added (4.1 g, 25.3 mmol). The mixture is stirred at 8O0C for about an extra 24 h and then concentrated under vacuum to give a semi-solid residue. 200 mL of water is added followed by a 10 N aqueous solution of NaOH (20 mL) and 200 mL of CH2CI2. After shaking the mixture for a few minutes, the solid is filtered over a pad of Celite.(R). and the filtrate is transferred into a separatory funnel. The organic layer is separated and the aqueous layer is extracted with CH2CI2. The combined organic extracts are washed with brine, dried (Na2SO4), filtered and concentrated under vacuum to give 3.69 g of a brown solid. This solid is triturated in hot CH3CN and filtered. The solid is discarded and the filtrate is concentrated under vacuum to give 2.3 g of a brown semi-solid. This material is purified on a CombiFlash.(R). Companion apparatus on 40 g silica gel column eluted with EtOAc/hexanes gradient. After evaporation of the solvent 13-152under vacuum, the desired compound 37c is isolated as a yellow solid (390 mg, 8percent yield).

The chemical industry reduces the impact on the environment during synthesis 823-57-4. I believe this compound will play a more active role in future production and life.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GmbH; WO2009/62308; (2009); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

The chemical industry reduces the impact on the environment during synthesis 104-11-0, name is 1-(4-Chlorophenyl)-N-methylmethanamine, I believe this compound will play a more active role in future production and life. 104-11-0

General procedure: A solution of 0.17g (1.40mmol) of N-benzylmethylamine, 0.20g (1.40mmol) of K2CO3 and 0.40g of (R,S)-3(4-bromobutyl)-5-phenyloxazolidin-2-one 23 in ACN was allowed to stirring under reflux for 6-12h and monitored by TLC until the reaction was completed. The hot solution was filtered and concentrated in vacuo to afford 0.29g (85.0mmol) of a chromatography pure yellow oil 2a.

The chemical industry reduces the impact on the environment during synthesis 104-11-0. I believe this compound will play a more active role in future production and life.

Reference:
Article; Zampieri, Daniele; Vio, Luciano; Fermeglia, Maurizio; Pricl, Sabrina; Wuensch, Bernhard; Schepmann, Dirk; Romano, Maurizio; Mamolo, Maria Grazia; Laurini, Erik; European Journal of Medicinal Chemistry; vol. 121; (2016); p. 712 – 726;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics