Month: August 2021

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. 39065-95-7, name is 4-(Chlorodifluoromethoxy)aniline, A new synthetic method of this compound is introduced below., category: chlorides-buliding-blocks

To a solution of 7-bromo-6-fluoro-1-isopropyl-1H-benzo[d]imidazole-5-carboxylic acid (20f, 70 mg, 0.232 mmol, 1 eq) in DMF (2 mL) was added HATU (106.07 mg, 0.279 mmol, 1.2 eq), 4-[chloro(difluoro)methoxy]aniline (1h, 49.50 mg, 0.256 mmol, 1.1 eq) and DIEA (90.13 mg, 0.697 mmol, 121.47 uL, 3 eq). The mixture was stirred at 50 C. for 3 hr. TLC (petroleum ether:ethyl acetate=1:1) indicated 20f consumed completely. The reaction mixture was concentrated under reduced pressure. The residue was diluted with H2O (10 mL) and extracted with EtOAc (10 mL*3). The combined organic layers were washed with brine (10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give the crude product. The residue was purified by column chromatography (SiO2, petroleum ether/ethyl acetate=10/1 to 1:1). Compound 20g was obtained as a white solid. 1H NMR (400 MHz, MeOD-d4) delta 8.57 (s, 1H), 8.01 (d, J=6.4 Hz, 1H), 7.82 (d, J=8.8 Hz, 2H), 7.30 (d, J=9.3 Hz, 2H), 5.70 (td, J=6.7, 13.6 Hz, 1H), 1.67 (d, J=6.8 Hz, 6H).

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; Terns, Inc.; ROMERO, F. Anthony; KIRSCHBERG, Thorsten A.; HALCOMB, Randall; XU, Yingzi; (144 pag.)US2020/87283; (2020); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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. 367-22-6, name is 4-Chloro-3-fluoroaniline belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Application In Synthesis of 4-Chloro-3-fluoroaniline

A mixture of 5-amino-3-methyl-1 ,2-thiazole-4-carboxylic acid [CAS-RN: 22131 -51-7, for the synthesis, please see: J. Goerdeler, H. Horn, Chem. Ber. (1963),96, 1551-1560.] (5.00 g, 9.93 mmol, 1.0 eq) and thionyl chloride (20.7 mL,284 mmol, 9.0 eq) was stirred at 80 C for 2 h. After cooling, the volatilecomponents were removed in vacuo. The crude acid chloride was diluted with toluene and concentrated at the rotary evaporator. This process was repeated one more time. The acid chloride (1.75 g, 9.93 mmol, 1.0 eq) observed this way was dissolved in THF (15 mL). Then, 4-chloro-3-fluoroaniline [CAS-RN: 367-22-6] (2.89 mL, 19.9 mmol, 2.0 eq) and triethyl amine (2.01 mL, 19.9 mmol, 2.0 eq)was added. The reaction mixture was stirred at rt overnight. After addition of water the crude reaction mixture was acidified with 1M hydrochloric acid and extracted with EtOAc. The organic phase was washed with brine and dried with sodium sulfate. After removal of the volatile components the product was crystallized from dichloromethane and methanol. The precipitate was isolated by filtration and dried under high vacuum to give the title compound (600 mg,-21% yield of theory based on the intermediate acid chloride).UPLC-MS (Method 2): Rt = 1.06 mm; MS (Elneg) m/z = 284 [M-H].1H-NMR (400 MHz, DMSO-d6): oe [ppm] = 2.36 (s, 3H), 7.28 (s br, 2H), 7.41 (dd,1H), 7.51 (t, 1H), 7.81 (dd, 1H), 9.82 (s, 1H).

The synthetic route of 367-22-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; BAeRFACKER, Lars; SIEMEISTER, Gerhard; HEINRICH, Tobias; PRECHTL, Stefan; STOeCKIGT, Detlef; ROTTMANN, Antje; WO2015/113927; (2015); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 15205-11-5, name is 2-Chloro-4-fluorobenzylamine, 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 15205-11-5, Product Details of 15205-11-5

Example 94 N-[(2-chloro-4-fluorophenyl)methyl]-1-cyclopentyl-5-oxoprolinamide (E94) 1-Cyclopentyl-5-oxoproline (0.100 g, 0.51 mmol, prepared as described below) was dissolved in a mixture of dichloromethane (2.5 ml) and dimethylformamide (0.5 ml) and to this were added N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (0.117 g, 0.61 mmol), 1-hydroxybenzotriazole (0.082 g, 0.61 mmol), and N-ethyl morpholine (0.2 ml, 1.52 mmol). The mixture was stirred for 10 minutes and then [(2-chloro-4-fluorophenyl)methyl]amine (0.097 g, 0.61 mmol) was added and the mixture was stirred overnight. Saturated aqueous sodium hydrogen carbonate (10 ml) was added and the mixture stirred vigorously for 15 minutes. The organic phase was separated with a phase separator and the aqueous phase was washed with further aliquots of dichloromethane (3*10 ml). The organic fractions were combined and dried over magnesium sulphate. The solvent was then evaporated and the residue was purified by mass-directed automated HPLC to give pure N-[(2-chloro-4-fluorophenyl)methyl]-1-cyclopentyl-5-oxoprolinamide. LC/MS [M+H]+=339, retention time=2.4 minutes.

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-Chloro-4-fluorobenzylamine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GLAXO GROUP LIMITED; US2008/9541; (2008); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Electric Literature of 2106-02-7, 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. 2106-02-7, name is 2-Chloro-4-fluoroaniline, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: 1 molar equivalent of the carboxylic acid obtained in the hydrolysis reaction (general procedure B) was introduced into a 25 mL round-bottom flask fitted with a condenser. The system was purged with an argon stream and 4 mL of SOCl2 (excess) were added. The reaction mixture was refluxed for 1 h, after which it was concentrated under reduced pressure and the crude acyl chloride was dissolved in dichloromethane. In parallel, 1.33 eq. of the corresponding aniline were dissolved in a 1:1 mixture of dichloromethane:pyridine (0.2 M). The resulting solution was added to the reaction mixture, which was then stirred for 12 h at rt. The solvents were removed under reduced pressure and the resulting crude mixture was purified by column chromatography on silica gel.

The chemical industry reduces the impact on the environment during synthesis 2-Chloro-4-fluoroaniline. I believe this compound will play a more active role in future production and life.

Reference:
Article; Bueno, Jose Maria; Carda, Miguel; Crespo, Benigno; Cunat, Ana Carmen; de Cozar, Cristina; Leon, Maria Luisa; Marco, J. Alberto; Roda, Nuria; Sanz-Cervera, Juan F.; Bioorganic and Medicinal Chemistry Letters; vol. 26; 16; (2016); p. 3938 – 3944;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Some common heterocyclic compound, 4152-90-3, name is (3-Chlorophenyl)methanamine, molecular formula is C7H8ClN, 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. SDS of cas: 4152-90-3

(a) N-(3′-chlorobenzyl)-2-cyanoacetamide A solution of 38.5 g. (0.34 mole) of ethyl cyanoacetate and 48.1 g. (0.34 mole) of 3-chlorobenzylamine in 120 ml. of 95% ethanol is refluxed for 5 hours and then allowed to stand overnight at ambient temperature. Agitation causes crystallization. Filtration is followed by washing of the solid with a small amount of ether to give 28.7 g. of the desired product as small, white needles, m.p. 123-5 C. The filtrate is evaporated in vacuo and a solid is obtained by trituration of the oily residue with ether. The solid is isolated by filtration, slurried in 900 ml. of deionized water, reisolated by vacuum filtration and dried to give an additional 11.9 g. of product, m.p. 122-4 C. yield: 40.6 g., 57% nu3300 (NH), 2270 (CN) and 1660 cm.-1 (C=O); delta 8.87 (broad t, 1H, NH), 7.4 (broad s, 4H, phenyl protons), 4.37 (d, 2H, benzyl methylene); and 3.7 (s, 2H, CH2 CO). Anal. Calc’d for C10 H9 ClN2 O: C,57.57;H,4.35;N,13.43;Cl,16.99; Found: C,57.94;H,4.36;N,13.42;Cl,77.21.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4152-90-3, its application will become more common.

Reference:
Patent; Rohm and Haas Company; US4028084; (1977); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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. 622-24-2, name is (2-Chloroethyl)benzene belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Formula: C8H9Cl

General procedure: A 10 mL Schlenk tube was charged with CoBr2 (6.6 mg, 0.03mmol), 1,3-diisopropyl-1H-benzimidazol-3-ium bromide (L4; 8.5mg, 0.03 mmol), 4-methoxy-N-[(1E)-1-phenylethylidene]aniline(1a, 67.6 mg, 0.30 mmol), 1-chlorooctane (2a, 76.5 muL, 0.45 mmol), and THF (0.69 mL). A 1.92 M solution of t-BuCH2MgBr inTHF (0.31 mL, 0.60 mmol) was added dropwise at 0 C, and themixture was stirred at r.t. for 6 h. The reaction was quenched by theaddition of 3 M aq HCl (1.0 mL), and the mixture was stirred at r.t.for 1 h, then extracted with EtOAc (3 × 10 mL). The organic layerswere combined, dried (MgSO4), and concentrated under reduced pressure. The crude product was purified by chromatography [silicagel, hexane-EtOAc (40:1)].

The synthetic route of 622-24-2 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Gao, Ke; Yamakawa, Takeshi; Yoshikai, Naohiko; Synthesis; vol. 46; 15; (2014); p. 2024 – 2039;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Related Products of 61881-19-4, 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. 61881-19-4 name is 2,2,2-Trifluoro-N-phenylacetimidoyl 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.

3.1.16 Methyl 4-O-acetyl-2,3-di-O-benzyl-alpha-d-galactopyranosyluronate-(1?2)-3,4-di-O-benzyl-alpha-l-rhamnopyranosyl 1-N-phenyltrifluoroacetimidate (26) To a solution of 25 (261 mg, 0.33 mmol) in dry THF/MeOH (5.0 mL/5.0 mL), PdCl2 (28 mg, 0.16 mmol) was added. After being stirred at room temperature for 5 h, the solution was filtered through Celite and concentrated under vacuum. The resulting syrup was purified by chromatography on silica gel (petroleum ether/ethyl acetate, 2.5:1) to provide the hemiacetal as a colorless syrup (236 mg, 95%). To a solution of the hemiacetal (216 mg, 0.28 mmol) in acetone (2.5 mL), K2CO3 (116 mg, 0.84 mmol), and N-phenyl trifluoroacetimidoyl chloride (118 mg, 0.56 mmol) were added. After stirring at ambient temperature for 4 h, the mixture was filtered and concentrated in vacuo. The resulting residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 6:1) to afford 26 (242 mg, 92%), which was used directly without characterization.

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

Reference:
Article; Ma, Yuyong; Cao, Xin; Yu, Biao; Carbohydrate Research; vol. 377; (2013); p. 63 – 74;,
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. 89794-02-5, name is 4-Bromo-2-chlorotoluene, A new synthetic method of this compound is introduced below., Computed Properties of C7H6BrCl

A degassed mixture of 4-bromo-2-chloro-l-methylbenzene (0.600 g, 2.92 mmol, Aldrich 528889), 2-(cyclopent-l-en-l-yl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (0.680 g, 3.50 mmol, Combi-Blocks, PN-2510), Na2C03 (2.0 M solution, 4.4 mL, 8.8 mmol) and [1,1′- bis(diphenylphosphino)ferrocene]palladium(II) dichloride complex with dichloromethane (162 mg, 0.198 mmol) in MeCN (5 mL) was heated in a sealed vial to 110 C in an oil bath for 3 hours. The reaction was cooled to room temperature and partitioned between EtOAc and water. The organic layer was washed with water, followed by brine, dried over Na2S04, filtered and concentrated. The product was purified by flash chromatography, eluting with a gradient from 0-50% EtOAc in hexanes (520 mg, 92%). NMR (400 MHz, CDC13) delta 7.42 (d, J= 0.9 Hz, 1H), 7.25 (dd, J = 7.9, 1.3 Hz, 1H), 7.17 (d, J = 7.9 Hz, 1H), 6.20 – 6.16 (m, 1H), 2.73 – 2.65 (m, 2H), 2.59 – 2.50 (m, 2H), 2.38 (s, 3H), 2.10 – 1.96 (m, 2H).

The synthetic route of 89794-02-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; INCYTE CORPORATION; DOUTY, Brent; BUESKING, Andrew W.; BURNS, David M.; COMBS, Andrew P.; FALAHATPISHEH, Nikoo; JALLURI, Ravi Kumar; LEVY, Daniel; POLAM, Padmaja; SHAO, Lixin; SHEPARD, Stacey; SHVARTSBART, Artem; SPARKS, Richard B.; YUE, Eddy W.; (355 pag.)WO2019/79469; (2019); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Some common heterocyclic compound, 61881-19-4, name is 2,2,2-Trifluoro-N-phenylacetimidoyl chloride, molecular formula is C8H5ClF3N, 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. Product Details of 61881-19-4

3.1.7 Methyl 4-O-acetyl-2,3-di-O-benzyl-alpha-d-galactopyranosiduronate 1-N-phenyltrifluoroacetimidate (7) Compound 17 (2.40 g, 5.4 mmol) was dissolved in AcOH (90 mL) and Ac2O (90 mL). The reaction mixture was cooled in an ice bath for 10 min, H2SO4 (0.9 mL) was then slowly added. The reaction was monitored by TLC (petroleum ether/ethyl acetate, 2:1) and showed completion after approximately 3 h. The reaction mixture was allowed to warm to rt during the progress of the reaction. NaOAc (9.2 g) was added and the mixture was stirred until all NaOAc had dissolved. The mixture was then evaporated to dryness, taken up in EtOAc, washed with H2O (extracted with EtOAc), dried over Na2SO4, filtered, evaporated to dryness, and finally co-evaporated three times with EtOH. The resulting syrup was purified by chromatography on silica gel (petroleum ether/ethyl acetate, 3:1) to provide a white solid (2.37 g, 93%, alpha and beta isomers were not separable). Ammonia gas was bubbled through a solution of the above product (2.16 g, 4.6 mmol) in a mixture of THF/CH3OH (v/v, 7: 3, 45 mL) cooled in an ice bath for 20 min. The solvent was then concentrated under reduced pressure to give a residue, which was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 2:1) to afford 18 (1.48 g, 75%) as a white solid. A suspension of hemiacetal 18 (472 mg, 1.1 mmol), K2CO3 (455 mg, 3.3 mmol), and N-phenyl trifluoroacetimidoyl chloride (457 mg, 2.2 mmol) in acetone (6.6 mL) was stirred at ambient temperature for 2 h. TLC showed the completion of the reaction. The mixture was filtered and concentrated in vacuo. The resulting residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 7:1) to afford 7 (570 mg, 87%), which was used directly without characterization.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 61881-19-4, its application will become more common.

Reference:
Article; Ma, Yuyong; Cao, Xin; Yu, Biao; Carbohydrate Research; vol. 377; (2013); p. 63 – 74;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Electric Literature of 874-17-9, A common heterocyclic compound, 874-17-9, name is 4-Chloro-2,6-dibromoaniline, molecular formula is C6H4Br2ClN, 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.

The RM-1 to RM-10 used for the synthesis of the objective compound are as follows:For the synthesis of the target compound, RM-11 was synthesized by the above reaction scheme.In a round bottom flask, 15.0 g of 2,6-dibromo-4-chloroaniline,(RM-1) were dissolved in 200 ml of 1,4-dioxane, 60 ml of K2CO3 (2M) and 3.64 g of Pd (PPh3) 4 were added, and the mixture was stirred under reflux. After confirming the reaction by TLC, water was added and the reaction was terminated.Then, 13.5 g of phenylboronic acid (RM-1) was dissolved in 200 ml of 1,4-dioxane, 60 ml of K2CO3 (2M) and 41.6 g of Pd (PPh3) were added thereto and the mixture was stirred under reflux. After confirming the reaction by TLC, water was added and the reaction was terminated. The organic layer was extracted with MC, filtered under reduced pressure, and then subjected to column purification to obtain 8 g of intermediate RM-11 (yield 70%).

The synthetic route of 874-17-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; DONGJIN SEMICHEM Co., Ltd.; Park Min-su; Ahn Hyeon-cheol; Kang Gyeong-min; Lee Hyeong-jin; Seo Jeong-a; Kim Seung-ho; (76 pag.)KR2019/11090; (2019); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics