Category: chlorides-buliding-blocks

Some common heterocyclic compound, 102-49-8, name is 3,4-Dichlorobenzylamine, molecular formula is C7H7Cl2N, 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. HPLC of Formula: C7H7Cl2N

Intermediate 15 N-(3,4-dichlorobenzyl)-7-methylimidazo[1,2-b]pyridazin-6-amine; To a mixture of 6-chloro-7-methylimidazo[1 ,2-b]pyridazine (0.20 g, 1.19 mmol) and 3,4-dichlorobenzylamine (0.24 ml_, 1.78 mmol) in 1 ,4-dioxane (7 ml_), were added sodium tert-butoxide (0.18 g, 1.91 mmol), (R)-(+)-2,2′- bis(diphenylphosphino)-1 ,1′-binaphthyl (0.06 g, 0.10 mmol) and tris(dibenzylideneacetone)dipalladium(0) (0.04 g, 0.06 mmol) at room temperature. The reaction mixture was heated at 1000C for 1 hour under microwave irradiation. The crude mixture was diluted with ethyl acetate/water and acidified with hydrochloric acid (2N) to pH 3, then extracted with ethyl acetate. The combined organic layers were dried (magnesium sulphate) and concentrated in vacuo. The crude mixture was purified by flash column chromatography (hexane/ethyl acetate 1 :4) followed by precipitation with diethyl ether to give N- (3,4-dichlorobenzyl)-7-methylimidazo[1 ,2-b]pyridazin-6-amine (0.25 g, 48percent yield) 1H NMR (300 MHz, CDCI3): delta 7.51 (1 H, s), 7.41 (2H, bs), 7.36 (1 H, s), 7.32 (1 H, d, J = 8.2 Hz), 7.15 (1H, dd, J = 2.3, 8.2 Hz), 4.47 (2H, d, J = 5.2 Hz), 4.43 (bs, 1 H), 2.14 (S, 3H). LCMS: 307 [M+1]. (MW: 307.2)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 102-49-8, its application will become more common.

Reference:
Patent; CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS (CNIO); WO2009/60197; (2009); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

363-51-9,Some common heterocyclic compound, 363-51-9, name is 2-Chloro-6-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) To a stirred suspension of (A7) as obtained from example 5 (60.0 g, 126 mmol) in acetonitrile (180 ml.) was added pyridine (35.6 ml_, 440 mmol) and 2-chloro-6-fluoroaniline (27.4 g, 188 mmol, CAS-no. 363-51-9 obtained from Combiblocks, product code OS-7812; alternatively a preparation of 2-chloro-6-fluoroaniline is described in US 4,089,958, example XVIII) at 22C. The cloudy solution was cooled to 0-5C and phosphoryl chloride (21.2 g, 138 mmol) was added over a period of 10 min. The reaction mixture was stirred for 1 h resulting in a clear solution. Methanol (360 ml.) and 85% phosphoric acid (12.8 ml_, 189 mmol) were added and the mixture was heated to 60C for 2 h. (0796) The reaction solvent was partially removed by distillation (95C bath, 64-72C internal temperature) to give 420 ml. distillate. The distillation residue was slowly cooled to 22C and stirred for 16 h. The resulting suspension was cooled to 0-5C and stirred for additional 2 h. The solid was isolated, washed two times with 2-propanol (30 ml.) and dried in vacuum at 50C for 16 h to give crude product Compound (I) as a white solid (55g, 106 mmol) in 84% yield. (0797) HPLC (method 1 ): Rt = 2.81 min (> 98% area) (0798) b) The reaction product (30.0 g, 57.6 mmol) was further purified by suspension in anhydrous ethanol (450 ml.) and heating to 60C. The resulting clear solution was filtered, the filter cake was washed two times with hot anhydrous ethanol (30 ml.) and the filtrate was concentrated by distillation of solvent (270 ml. distillate) at 100C bath temperature. The solution was cooled to 50C, seeded (I) (0.3 g), and cooled stepwise to 0-5C over 4h. The precipitated solid was isolated, washed two times with anhydrous ethanol (15 ml.) and dried in vacuum at 50C for 16h to give Compound (I) as a white solid (25.7 g, 49.3 mmol) in 86% yield from crude (0799) Compound (I). (0800) HPLC (method 1 ): Rt = 2.81 min (> 99% area) (0801) 1H NMR (400 MHz, DMSO-d6) d ppm 1.29 (t, J=7.15 Hz, 3 H) 1.45 (d, J=6.36 Hz, 3 H) 3.80 (q, J= 7.09 Hz, 2 H) 4.44 – 4.55 (m, 2 H) 5.36 (dt, J=12.78, 6.33 Hz, 1 H) 5.80 (t, J= 5.75 Hz, 1 H) (0802) 7.30 – 7.47 (m, 3 H) 7.50 – 7.66 (m, 2 H) 10.05 (s, 1 H) (0803) LCMS (method 1 ): Rt = 0.90 min; MS (ESIpos): m/z = 521 (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 363-51-9, its application will become more common.

Reference:
Patent; BAYER AKTIENGESELLSCHAFT; BAYER PHARMA AKTIENGESELLSCHAFT; HASSFELD, Jorma; GRADL, Stefan, Nikolaus; RUBENBAUER, Philipp; VAN DER HAAS, Henricus, Nicolaas, Sebastian; GIELING, Reinerus, Geradus; (127 pag.)WO2019/197239; (2019); 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. 202925-07-3, name is 2-Chloro-1-fluoro-4-methoxybenzene, A new synthetic method of this compound is introduced below., name: 2-Chloro-1-fluoro-4-methoxybenzene

A mixture of 3-chloro-4-fluoroanisole (2.52 g, 15.7 mmol, 1.0 eq.), silver trifluoroacetate (8.53 g,38.6 mmol, 2.5 eq.), iodine (7.94 g, 31.3 mmol, 2.0 eq.) and chloroform (100 mL) is stirred at r.t. for 16 h. The reaction mixture is filtered through a silica plug on a fritted funnel and rinsed with chloroform. The filtrate is washed successively with an aqueous solution of Na2S2O3, water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue is purified by flash chromatography on silica gel to afford the expected product.

The synthetic route of 202925-07-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GALAPAGOS NV; LES LABORATOIRES SERVIER; LABEGUERE, Frederic, Gilbert; HENG, Rama; ALVEY, Luke, Jonathan; AMANTINI, David; BREBION, Franck, Laurent; DE CEUNINCK, Frederic, Andre; DEPREZ, Pierre, Marc, Marie, Joseph; GOSMINI, Romain, Luc, Marie; JARY, Helene; PEIXOTO, Christophe; POP-BOTEZ, Iuliana, Ecaterina; VARIN, Marie, Laurence, Claire; (147 pag.)WO2017/211667; (2017); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 104-52-9,Some common heterocyclic compound, 104-52-9, name is 3-Phenylpropyl Chloride, molecular formula is C9H11Cl, 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 compound 6 (0.06mmol) in 2 ml DMF was added potassium carbonate (0.18 mmol). The mixture was heated to 90 C and l-(2- chloroethyl)piperidine hydrochloride (0.066 mmol) was added. The reaction mixture was then stirred at 90 C for two hours. After the reaction was completed, the mixture was poured into 50 ml water and then extracted with dichloromethane (50 ml x 3). The organic layer was dried with anhydrous Na2S04 and evaporated to dryness under reduced pressure to give the crude product, which was further purified by flash silica gel column chromatography (methanol : dichloromethane = 1:12) to give a light yellow paste (yield 63%).

The synthetic route of 104-52-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; UNIVERSITY OF FLORIDA RESEARCH FOUNDATION, INCORPORATED; LI, Chenglong; MAO, Liguang; (0 pag.)WO2019/165158; (2019); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 210532-25-5, 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. 210532-25-5 name is 3,5-Difluorobenzene-1-sulfonyl chloride, 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.

(R)-N2-Indan-1-yl-4H-benzo[d][1,3]oxazine-2,5-diamine (example 2) (150 mg, 0.54 mmol) was dissolved in 5 mL pyridine and 3,5-difluoro-benzenesulfonyl chloride (112 mg, 0.53 mmol) was added. The reaction mixture was stirred at room temperature overnight. 1N HCl was added until pH5. The mixture was extracted three times with ethyl acetate (50 mL each). The organic phases ware pooled, dried with sodium sulfate, filtered and evaporated. The crude product was purified by a silica gel column chromatography with heptane/ethyl acetate 1:1 to give a white solid (24 mg, 9%), MS: m/e=456.0 (M+H+).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3,5-Difluorobenzene-1-sulfonyl chloride, and friends who are interested can also refer to it.

Reference:
Patent; Kolczewski, Sabine; Roche, Olivier; Steward, Lucinda; Wichmann, Juergen; Woltering, Thomas; US2010/63042; (2010); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

1940-27-8, name is 4-Bromo-2,5-dichloroaniline, 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: 1940-27-8

General procedure: A mixture of corresponding chloro derivative (IV) (4.2 mmol), the appropriate amine (4.2 mmol) and triethylamine (8.4 mmol) in dry acetonitrile was refluxed for 4 hours. The mixture was cooled, poured on crushed ice and filtered. The residue was washed with cold water and dried. The crude product was recrystallized from ethanol to get the titled compounds.

The synthetic route of 1940-27-8 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Pradeep Kumar; Joshi, Shrinivas D.; Dixit, Sheshagiri R.; Kulkarni; Indian Journal of Heterocyclic Chemistry; vol. 25; 1; (2015); p. 75 – 82;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 83121-15-7, The chemical industry reduces the impact on the environment during synthesis 83121-15-7, name is 3,5-Dichloro-2,4-difluoroaniline, I believe this compound will play a more active role in future production and life.

Example 3 2,4-Difluoro-3,5-dichlorophenyl isocyanate Hydrogen chloride was passed into a well-stirred solution of 39.6 gm (0.20 mol) of 2,4-difluoro-3,5-dichloroaniline in 400 ml of toluene until a precipitate no longer separated out. The heterogeneous mixture thus obtained was cooled to 5 to 10 C. At this temperature, 40 gm (0.4 mol) of phosgene were passed in, with stirring. The mixture was then heated slowly, with stirring, so that after about two hours a temperature of 100 to 105 C. was reached. Stirring was then continued for seven hours at this temperature. During this time, a clear solution was formed, and hydrogen chloride was liberated. Nitrogen was then passed into the mixture for one hour at the same temperature to drive off the excess phosgene. Thereafter the solvent was distilled off, in vacuo at the end. The crude product which remained was distilled in a water pump vacuum. Yield: 35.4 gm (0.158 mol; 79% of theory), B.p.: 100-104 C./20 mbar.

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, 3,5-Dichloro-2,4-difluoroaniline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Celamerck GmbH & Co. KG; US4457943; (1984); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 452-83-5,Some common heterocyclic compound, 452-83-5, name is 2-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.

Step 1: 5-Fluoro-8 chloroquinoline To a mixture of (5.0 g) 2-chloro-5-fluoroaniline (commercially available, 6.0 g), glycerol (6.0 g) and m-nitrobenzene sulfonic acid sodium salt (11.0 g), was added 20 mL of 70% sulfuric acid dropwise. The reaction temperature was raised to 140 C. for 2 h. The mixture was then cooled, poured on ice water and filtered through Celite. The filtrate was neutralized with NaOH and extracted with CH2Cl2. The combined organic layers were dried over anhydrous MgSO4 and concentrated on a rotary evaporator. The crude product was purified by flash chromatography on silica gel using 100% CH2Cl2 to give 3.7 g of the desired product of a yellow solid; MP=74-76 C.; MS (ES) m/z (relative intensity): 182 (M+H)+ (100).

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

Reference:
Patent; Wyeth; US2007/299083; (2007); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Some common heterocyclic compound, 60811-18-9, name is 4-Bromo-1-chloro-2-fluorobenzene, molecular formula is C6H3BrClF, 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. name: 4-Bromo-1-chloro-2-fluorobenzene

[Example 23] (Preparation of 4′-(trans-4-n-pentyl-4-silacyclohexyl)-4-chloro-3-fluorobiphenyl) 6.5 g (20 mmol) of p-(trans-4-n-pentyl-4-silacyclohexyl) bromobenzene was dripped into a mixture of 0.5 g of magnesium (21 mmol) and 30 ml of THF to obtain a Grignard’s reagent. This solution was then dripped into a 50 ml THF solution of 4.2 g (20 mmol) of 4-chloro-3-fluoro-1-bromobenzene and a catalytic amount of tetrakis (triphenylphosphine) palladium (0) to obtain 4′-(trans-4-n-pentyl-4-silacyclohexyl)-4-chloro-3-fluorobiphenyl. This was then purified by means of chromatography to obtain 6.8 g of the target product (yield 98%). IR (liquid film) numax: 2953, 2916, 2870, 2108, 1479, 1396, 1200, 985, 879 and 812 cm-1

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 60811-18-9, its application will become more common.

Reference:
Patent; Shin-Etsu Chemical Co., Ltd.; US5659059; (1997); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 627-42-9,Some common heterocyclic compound, 627-42-9, name is 2-Methoxyethyl chloride, molecular formula is C3H7ClO, 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.

Sodium iodide (0.191 g, 1.273 mmol) was added to a stirred suspension of 5-fluoro-2- nitrophenol (4 g, 25.5 mmol), potassium carbonate (10.56 g, 76 mmol) and l-chloro-2- methoxyethane (5.1O mL, 56.0 mmol) in DMF (102 mL) at room temperature. The reaction mixture was allowed to stir at 800C overnight. Further l-chloro-2-methoxyethane (6.38 mL, 70.0 mmol) was added and the reaction mixture was allowed to stir at 800C for 4 h. Water and ethyl acetate were added and the organic layer was separated. The aqueous layer was neutralised with 1 N hydrochloric acid and extracted with ethyl acetate. The combined organic layers were washed with water, dried (MgSO4), filtered and evaporated to give a yellow oil. Column chromatography (petroleum ether/ethyl acetate 6:1) gave 4-fluoro-2-(2-methoxyethoxy)-l -nitrobenzene as a clear oil (2.26g, 39%).

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

Reference:
Patent; BIAL-PORTELA & COMPANHIA, S.A.; WO2009/84970; (2009); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics