Author: Jessica.F

Electric Literature of 454-78-4,Some common heterocyclic compound, 454-78-4, name is 2-Bromo-1-chloro-4-(trifluoromethyl)benzene, molecular formula is C7H3BrClF3, 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: To a 500 mL three-neck RBF equipped with a magnetic stirring bar were added, under N2 atmosphere, 3-bromo-4-chloro-benzotrifluoride (16.5 mL, 110 mmol) and dry THF (150 mL). The resulting solution was cooled to 0 C. To this solution was added z’-PrMgBr (110 mL, 110 mmol) and the reaction was warmed to rt and stirred for 1 h. To another 500 mL RBF containing a solution of CuBr Me2S (18.8 g, 91.5 mmol) in THF (100 mL) was added BF3*OEt2 (14 mL, 110 mmol) dropwise at -40 C. The resulting solution was stirred at that temperature for 45 min. Then, the Grignard reagent prepared previously was added dropwise to this solution while maintaining the internal temperature at -32 to -38 C. After completion of addition, the reaction mixture was stirred at that temperature for 1 h. The reaction mixture was cooled to -78 C, and a solution of (2S)-l-t-butyl 2-ethyl 5-methoxypyrrolidine-l ,2- dicarboxylate (25.0 g, 91.5 mmol) in THF (50 mL) was added dropwise. The resulting reaction mixture was allowed to warm up to rt and was stirred for 14 h. The reaction mixture was cooled to 0 C, and saturated aqueous NH4C1 solution (100 mL) was added followed by aqueous NH4OH solution (100 mL) and water (300 mL). The layers were separated. The aqueous layer was extracted with EtOAc (3 x 200 mL). The combined organics were dried over anhydrous Na2S04 and concentrated. The crude product was purified by column chromatography eluting with 5% EtOAc in petroleum ether to yield (2S,5S)-l-tert-butyl 2-ethyl 5-(2-chloro-5- (trifluoromethyl)phenyl)pyrrolidine-l,2-dicarboxylate (34.0 g, 79.8 mmol) as a colorless liquid. 1H NMR (400 MHz, CDC13) 7.32-7.47 (m, 3 H), 5.39-5.50 (m, 1 H), 4.58-4.70 (m, 1 H), 4.22- 4.28 (m, 2 H), 2.55 (m, 1 H), 2.18 (m, 1 H), 2.05 (m, 1 H), 1.83 (m, 1 H), 1.16-1.43 (m, 12 H); LC-MS ESI calc’d. for Ci9H23ClF3N04 [M-Boc]+ 321.84, found 322.2.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Bromo-1-chloro-4-(trifluoromethyl)benzene, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; LIU, Jian; SHAO, Pengcheng Patrick; KRIKORIAN, Arto, D.; VACHAL, Petr; WO2015/17302; (2015); A2;,
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. 167404-32-2, name is 4-Cyclopropylbenzene-1-sulfonyl chloride belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Application In Synthesis of 4-Cyclopropylbenzene-1-sulfonyl chloride

In a flame dried flask under N2 blanket, compound D (1.5 g, 4.9 MMOL) was dissolved in dry THF (30 mL) and COOLED TO-78C. N-BUTYL lithium (1.9 M in hexanes, 5.4 mL, 9.7 MMOL) was added followed after 45 min by compound E (1.27 g, 6.3 MMOL). The cold bath was removed after 2 h and the reaction mixture was allowed to warm to rt over 45 minutes then quenched with aq NH4CI. EtOAc (30 mL) was added to dilute the reaction mixture. The reaction mixture was washed with brine (100 mL x 2). The organic layer was dried over NA2SO4 and then concentrated to dryness. The crude material was purified via sgc (25% EtOAc/Hexanes) to give 545 mg (27%) of compound F. Compound i (120 g, 1.0 mml) was dissolved in CH2CI2 (1.2 L) with HG20 (6.0 g, 14.4 MMOL) and K2CO3 (24.0 g, 0.17 mol) and cooled to-30 C. Br2 (85.2 g, 1.1 mol) was added over 10 min period of time. The reaction mixture was stirred at-30 C for 4.5 h. The reaction mixture was washed with H20 (1 L) and brine (1 L). The organic layer was dried over NA2SO4 and concentrated to dryness. The crude material was distilled under reduced pressure to give 103.8 g (52%) of compound ii. In a flame dried flask under N2 blanket, compound ii (6.0 g, 30.5 MMOL) was dissolved in dry THF (30 mL) and cooled TO-78 C. A solution of n-butyl lithium (1.75 M in hexanes, 17.4 mL, 30.5 MMOL) was added and the reaction mixture was stirred for 20 min. S02 was bubbled in the reaction for 20 min. It was slowly warmed up to rt. CH2CI2 (50 mL) was added and the mixture was reacted with NCS (5.0 g, 37.4 MMOL) at rt overnight. The reaction mixture was washed with brine (100 mL x 2). The organic layer was dried over NA2SO4 and then concentrated to dryness. The crude material was purified via sgc (5% EtOAC/Hexanes) to give 3.65 g (55%) of compound II. To a round-bottom flask was added compound iii (3.0 g, 13.8 MMOL) and KF (2.4 g, 41.4 MMOL) followed by addition of acetone (50 mL) and water (30 mL). The reaction mixture was stirred at room temperature overnight. The solvent was then removed. Methylene chloride (40 mL) was added and it was washed with brine (40 mL). The organic layer was dried over NA2SO4 and then concentrated to dryness to give 2.77 g (100%) of compound E.

The synthetic route of 167404-32-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SCHERING CORPORATION; WO2004/48322; (2004); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Related Products of 64473-35-4, 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. 64473-35-4 name is 1-(3-Bromopropyl)-4-chlorobenzene, 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.

Step 1 3-(4-Chlorophenyl)propylamine The potassium salt of phthalimide (4.4 g, 24 mmol) was dissolved in DMF (20 ml) and 1-chloro-4-(3-bromopropyl)benzene (4.67 g, 20 mmol) was added. The mixture was stirred at 80 C. for 16 hours. Water (50 ml) and DCM (50 ml) were added, the phases were separated and the aqueous phase extracted with DCM (2*50 ml). The combined organic phases were washed with sodium hydroxide (0.2 M, 50 ml), dried (magnesium sulphate), filtered and concentrated in vacuo. Ethanol (75 ml) and hydrazine hydrate (2 equiv.) were added and the mixture was heated to reflux for 2 hours. After cooling the mixture was filtrated and the filter cake washed with DCM (2*50 ml). The filtrate and washings were evaporated and dissolved in ethyl acetate (40 ml). Washing of the organic phase with sodium hydroxide (0.4 M, 2*25 ml) and water (2*25 ml) followed by drying (magnesium sulphate), filtration and evaporation gave 3-(4-chlorophenyl)propylamine. 1H NMR (CDCl3): delta1.82-1.50 (m, 4H); 2.78-2.53 (m, 4H); 7.32-6.96 (m, 4H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-(3-Bromopropyl)-4-chlorobenzene, and friends who are interested can also refer to it.

Reference:
Patent; Andersen, Knud Erik; Dorwald, Florencio Zaragiza; Peschke, Bernd; Sidelmann, Ulla Grove; Rudolf, Klaus; Stenkamp, Dirk; Hurnaus, Rudolf; Muller, Stephan Georg; Krist, Bernd; Eriksen, Birgitte; US2002/58659; (2002); 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. 2770-01-6, name is 4-Chloro-1H-imidazo[4,5-c]pyridine, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C6H4ClN3

Reference Example 11 3-{[2-(Trimethylsilyl)ethoxy]methyl}-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one 1-{[2-(Trimethylsilyl)ethoxy]methyl}-1,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one [Show Image] Diethoxymethyl acetate (15 mL) was added to 2-chloropyridine-3,4-diamine (480 mg) and the resulting mixture was stirred at room temperature for 12 hours. To the mixture was added 1N hydrochloric acid and the precipitate formed was filtered, washed with diethyl ether and then dried to obtain a crude product (400 mg), 4-chloro-1H-imidazo[4,5-c]pyridine as a brown solid. The spectrum of this compound is as follows: 1H NMR (400 MHz, CD3OD) delta 9.45 (s, 1H), 8.51 (d, J = 5.9 Hz, 1H), 7.94 (d, J = 5.9 Hz, 1H). MS (ESI+) 154 (M+ +1, 100%). A hydrochloric acid/methanol solution (25 mL, methanol component 80-90%) was added to this solid (220 mg) and the resulting mixture was heated under reflux for 30 hours. The reaction solution was cooled to room temperature and concentrated under reduced pressure, and the resulting residue was washed with diethyl ether and dried to obtain a crude product (150 mg), 3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one as a brown solid. The spectrum of this compound is as follows: 1H NMR (400 MHz, CD3OD) delta 9.40 (s, 1H), 7.58 (d, J = 7.2 Hz, 1H), 6.87 (d, J = 7.2 Hz, 1H). MS (ESI+) 136 (M++1, 100%). Under a nitrogen atmosphere, sodium hydride (134 mg, a 60% oil dispersion) was added to N,N-dimethylformamide (15 mL) and the resulting suspension was cooled to -15C. To the suspension was added 3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one (360 mg) and the resulting mixture was stirred at room temperature for 30 minutes. Then, chloro-2-(trimethylsilyl)ethoxymethane (0.550 mL) was added dropwise thereto, followed by stirring at room temperature for 20 hours. Water was added to the reaction solution, followed by extraction with chloroform. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: chloroform/methanol = 20/1 to 10/1) to obtain 3-{[2-(trimethylsilyl)ethoxy]methyl}-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one (119 mg) and 1-{[2-(trimethyl-silyl)ethoxy]methyl}-1,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one (113 mg) each as a white solid. 3-{[2-(Trimethylsilyl)ethoxy]methyl}-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one 1H NMR (400 MHz, CDCl3) delta 11.49 (bs, 1H), 8.03 (s, 1H), 7.16 (m, 1H), 6.77 (d, J = 7.0 Hz, 1H), 5.91 (s, 2H), 3.66 (t, J = 8.2 Hz, 2H), 0.93 (t, J = 8.2 Hz, 2H), – 0.04 (s, 9H). MS (ESI+) 266 (M++1, 100%). 1-{[2-(Trimethylsilyl)ethoxy]methyl}-1,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one 1H NMR (400 MHz, CDCl3) delta 10.97 (bs, 1H), 7.84 (s, 1H), 7.21 (m, 1H), 6.56 (d, J = 7.1 Hz, 1H), 5.45 (s, 2H), 3.51 (t, J = 8.2Hz, 2H), 0.90 (t, J = 8.2 Hz, 2H), – 0.03 (s, 9H). MS (ESI+) 266 (M++1, 100%).

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 2770-01-6.

Reference:
Patent; Dainippon Sumitomo Pharma Co., Ltd.; EP1690863; (2006); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

54730-35-7, name is 3,5-Dichloro-4-methylaniline, 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. category: chlorides-buliding-blocks

Transferred 3,5-dichloro-4-methylaniline (0.28 g, 1.59 mmol, Eq: 1.00) to a 50-mL round-bottomed flask using dichoromethane (10 mL). Added Iota,Gamma-thiocarbonyldiimidazole (429 mg, 2.41 mmol, Eq: 1.51) and stirred overnight at room temperature. HPLC showed no starting material remaining. Concentrated the reaction mixture onto silica. Purified using a 12 g silica column on an Intelliflash 280; collected peaks only in 9 mL fraction at 32 mL/min; equilibrated with heptane; dry loaded; eluted 1 min with heptane; increased from 0 – 10%> dichloromethane/heptane over 5 min. Obtained 226 mg (65%) of l,3-dichloro-5-isothiocyanato- 2-methylbenzene as a yellow solid.

The synthetic route of 54730-35-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; BILOTTA, Joseph Anthony; CHEN, Zhi; CHIN, Elbert; DING, Qingjie; ERICKSON, Shawn David; GABRIEL, Stephen Deems; KLUMPP, Klaus; MA, Han; MERTZ, Eric; PLANCHER, Jean-Marc; WEIKERT, Robert James; WO2014/6066; (2014); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 54730-35-7, The chemical industry reduces the impact on the environment during synthesis 54730-35-7, name is 3,5-Dichloro-4-methylaniline, I believe this compound will play a more active role in future production and life.

To a solution of HBr (40% in water, 3.4 mL) in water (3 mL) was added 3,5-dichloro-4-methylaniline (2.0 g, 11.4 mmol). The suspension was heated to dissolve as much of the solid as possible, then the mixture was cooled to 0 degrees C. and a solution of sodium nitrite (0.83 g, 12.0 mmol) in water (2 mL) was added dropwise (temperature was maintained <5 degrees C.). After 10 min., the diazonium salt mixture was poured into a mixture of CuBr (8.2 g, 57.0 mmol) in 40% aq. HBr (13 mL) at room temperature. The resulting mixture was heated at 50 degrees C. for 45 min., then cooled to room temperature. The mixture was diluted with water and extracted with dichloromethane (3¡Á). The combined organics were filtered through Celite and dried over sodium sulfate, then concentrated in vacuo to provide the product, 5-bromo-1,3-dichloro-2-methylbenzene, as an orange solid. 1H NMR (400 MHz, CDCl3) delta 2.40 (s, 3H), 7.43 (s, 2H). 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-4-methylaniline, other downstream synthetic routes, hurry up and to see. Reference:
Patent; Diaz, Caroline Jean; Haffner, Curt Dale; Speake, Jason Daniel; Zhang, Cunyu; Mills, Wendy Yoon; Spearing, Paul Kenneth; Cowan, David John; Green, Gary Martin; US2010/222345; (2010); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Related Products of 54773-19-2,Some common heterocyclic compound, 54773-19-2, name is 1,2-Dichloro-3-(trifluoromethyl)benzene, molecular formula is C7H3Cl2F3, 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.

2,3-dichlorobenzotrifluoride 215 g (1.00 mol) of the compound of the formula (II), anhydrous potassium fluoride 140 g (2.41 mol), sulfolane 2000 mL,10 g of tetraphenylphosphonium bromide was introduced into the autoclave in batches, and the temperature was raised to 250-300 C for 20 hours under stirring. After cooling, the formed potassium chloride and excess potassium fluoride were removed by filtration.The filtrate is rectified, and a fraction of 112 C to 119 C is collected to obtain a compound of formula (III) 2,3-difluorobenzotrifluoride; The residue is further subjected to rectification to collect a fraction of 145 C – 151 C to obtain a by-product 2-fluoro-3-chlorobenzotrifluoride; the by-product can be recycled.The average yield of 2,3-difluorobenzotrifluoride, which is a continuous preparation of the compound of formula (III) after application, is 87.6%.

The synthetic route of 54773-19-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Nanjing Zheng Rong Pharmaceutical And Chemical Co., Ltd.; Chen Zhengwei; Xiao Tao; Zhu Jiahao; Yu Chuanzong; Dai Jianxin; (13 pag.)CN104693080; (2016); B;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 16429-44-0, 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. 16429-44-0, name is 5-Bromo-3-chlorobenzene-1,2-diamine, This compound has unique chemical properties. The synthetic route is as follows.

5-bromo-3-chloro-1 ,2-diaminobenzene (4.6 g; 20 mmol; 1 .0 eq.) was dissolved in EtOH (200 ml_) and then 2,3-dihydroxy-1 ,4-dioxane (2.5 g, 20 mmol; 1 .0 eq.) was added. The mixture was stirred for 4 h at RT and a second portion of 2,3-dihydroxy-1 ,4-dioxane (1 .3 g; 10 mmol; 0.5 eq.) was added. After stirring for 24 h at rt, RM was concentrated in a rotary evaporator and the residue was purified by FCC to provide 7-bromo-5- chloroquinoxaline (Intermediate 3) as a beige solid (4.7 g; yield 92 %; 98 % by UPLC).

The chemical industry reduces the impact on the environment during synthesis 5-Bromo-3-chlorobenzene-1,2-diamine. I believe this compound will play a more active role in future production and life.

Reference:
Patent; MERCK PATENT GMBH; BUCHSTALLER, Hans-Peter; (101 pag.)WO2018/87021; (2018); 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. 208186-78-1, name is 1,2-Dibromo-5-chloro-3-fluorobenzene, A new synthetic method of this compound is introduced below., Safety of 1,2-Dibromo-5-chloro-3-fluorobenzene

GammaAlpha1 2-Bromo-4-chloro-6-fluoro-benzaldehydeTo a solution of l,2-dibromo-5-chloro-3-fluoro-benzene (10 g, 34.68 mmol) in heptane (27 ml) was added THF (44 ml) and the mixture was cooled to -45 C. Then, iPrMgCl (38.14 ml, 38.14 mmol, 1M solution in THF) was added dropwise to the reaction mixture maintaining the temperature between -40 C to -45 C. The mixture was stirred for 30 minutes at -40 C before DMF (13.4 ml, 173.4 mmol) was added dropwise to the reaction mixture maintaining the temperature between -45 C to -20 C. After stirring for another 15 minutes at -20 C, it was poured into a mixture of 2N HC1 (20 ml) and ether (50 ml) at 0 C. The organic layer was separated and the aqueous layer was extracted two times with ether. The combined organic layers were dried with Na2S04 and evaporated in vacuo to obtain the title compound (7.8 g, 95%) as yellow solid.

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; F. HOFFMANN-LA ROCHE AG; AEBI, Johannes; BINGGELI, Alfred; HERTEL, Cornelia; KONKAR, Anish Ashok; KUEHNE, Holger; KUHN, Bernd; MAERKI, Hans P.; WANG, Haiyan; WO2012/101011; (2012); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 320-51-4, These common heterocyclic compound, 320-51-4, name is 4-Chloro-3-(trifluoromethyl)aniline, 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 S 1-Chloro-4-fluoro-2-(trifluoromethyl)benzene 4-Chloro-3-(trifluoromethyl)benzenamine (19.5 g, 100 mmoles), water (40 ml) and c.hydrochloric acid (40 ml) were heated with stirring on a steam bath until a white solid formed. The mixture was cooled (ice-salt bath) and a solution of sodium nitrite (7 g, 101 mmoles) in water (15 ml) was added over 15 mins. After stirring for a further hour at 0, tetrafluoroboric acid (30 g of 40% aqueous solution) was added dropwise over 15 minutes. After one hour the solid was filtered off, washed with water (10 ml), methanol (30 ml) and ether (30 ml) and then dried in vacuo. The dry compound was heated at 140-180 until no more fumes were observed. The cooled residue was dissolved in ethyl acetate, washed with 5% aqueous sodium hydroxide, dried Na2 SO4) and the solvent was removed in vacuo. The residue was distilled in vacuo (12 mmHg, oven temperature 50-55) to give the sub-title compound as a colourless oil (7.5 g). M+ 200/198; nmr (CDCl3)delta7.8-7.2 (m).

The synthetic route of 320-51-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Fisons plc; US4607041; (1986); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics