Tag: M.W=200-300

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. 54314-84-0, name is ((3-Bromopropoxy)methyl)benzene, A new synthetic method of this compound is introduced below., COA of Formula: C10H13BrO

[(3-Benzyloxy-propyl)-ethoxy-phosphinoylmethyl]-phosphonic acid diethyl ester To an oven-dried flask was added 10.25 g (44.7 mmol) of (3-Bromo-propoxymethyl)-benzene and 7.67 mL (44.7 mmol) of triethyl phosphite. The flask was fitted with a short-path distillation head, for removal of bromoethane, and the mixture heated at 150¡ã C. for 4 h. The reaction was cooled to ambient temperature, and then diluted with 120 mL of absolute ethanol and 1.8 N KOH (120 mL, 216 mol). The distillation head was replaced with a reflux condenser and the solution heated at reflux for 5 h. The reaction was cooled then concentrated in vacuo. The basic aqueous layer was extracted with EtOAc (2*) and then acidified to pH 3 with conc. HCl. The aqueous layer was extracted with EtOAc (3*) and the combined extracts were dried over MgSO4 and concentrated. The resulting crude product (8.24 g) was used as is in the next reaction. 31P NMR (300 MHz, DMSO-d6) delta34.113.

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; Metcalf III, Chester A.; Shakespeare, William C.; Sawyer, Tomi K.; Wang, Yihan; Bohacek, Regine; US2003/114486; (2003); A1;,
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Adding a certain compound to certain chemical reactions, such as: 1462-37-9, name is ((2-Bromoethoxy)methyl)benzene, belongs to ethers-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 1462-37-9, Formula: C9H11BrO

Methyl 1-(2-(benzyloxy)ethyl)-3-cyclohexyl-1H-indole-6-carboxylate. Intermediate 4 (1.029 g, 4.0 mmol) was added to a suspension of NaH (192 mg of 60percent dispersion in mineral oil, 4.8 mmol) in DMF (5 mL). The reaction mixture was stirred at room temperature for 15 minutes, treated with benzyl 2-bromoethyl ether (0.7 mL, 4.4 mmol), stirred at room temperature for 2 hours, quenched with water, and extracted with ethyl acetate (2.x.50 mL). The organic layers were combined and washed (1N HCl), dried (MgSO4), filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, 3:1 hexanes/ethyl acetate) to provide the desired product as a colorless thick oil (1.19 g, 76percent yield). MS m/z 392(MH+); 1H NMR (500 MHz, CDCl3) delta 1.31 (m, 1H), 1.45 (m, 4H), 1.80 (d, J=13.12 Hz, 1H), 1.87 (m, 2H), 2.10 (m, 2H), 2.84 (m, 1H), 3.79 (t, J=5.34 Hz, 2H), 3.94 (s, 3H), 4.33 (t, J=5.49 Hz, 2H), 4.45 (s, 2H), 7.12 (s, 1H), 7.20 (m, 2H), 7.27 (m, 3H), 7.66 (d, J=8.55 Hz, 1H), 7.78 (d, J=8.55 Hz, 1H), 8.08 (s, 1H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, ((2-Bromoethoxy)methyl)benzene, and friends who are interested can also refer to it.

Reference:
Patent; Hudyma, Thomas W.; Zheng, Xiaofan; He, Feng; Ding, Min; Bergstrom, Carl P.; Hewawasam, Piyasena; Martin, Scott W.; Gentles, Robert G.; US2006/46983; (2006); A1;,
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Reference of 19056-40-7, 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. 19056-40-7, name is 4-Bromo-3-methoxyaniline, This compound has unique chemical properties. The synthetic route is as follows.

b 5-Amino-2-bromo-phenol A suspension of 4-bromo-3-methoxy-phenylamine (37.6 g, 0.186 mol) and tetrabutylammonium iodide (96 g, 0.260 mol) in dichloromethane (1.2 L) was cooled down to -78 C. A 1M solution of boron trichloride in dichloromethane (520 mL, 0.521 mol) was added dropwise, within 20 min. The cooling bath was removed. After 3 hours, the reaction mixture was poured onto ice water (4.5 kg). The organic layer was extracted with water. The combined aqueous layers were washed with dichloromethane. The pH was adjusted to 9 using sodium hydrogencarbonate. Sodium chloride was added until saturation. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and the solvents were evaporated. The solid was washed with dichloromethane and dried under vacuum. 35.2 g of the title compound were obtained. Brown solid, ISP-MS: m/e=189.1 ([M+H]+).

The chemical industry reduces the impact on the environment during synthesis 4-Bromo-3-methoxyaniline. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Klug, Michael G.; Mattei, Patrizio; Mueller, Werner; Neidhart, Werner; Nettekoven, Matthias Heinrich; Pflieger, Philippe; Plancher, Jean-Marc; US2003/158179; (2003); A1;,
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Reference of 458-50-4, 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 458-50-4 as follows.

To a dry and N2 flashed flask was added 4-bromo-3-fluoroanisole (1.04 g, 5.07 mmol) in THF (6 mL) under N2. This was cooled to -78 ¡ãC, and n-BnLi (1.72 mL, 4.29 mmol) was added. The reaction was stirred at -78 ¡ãC for 30 min. The mixture above was added via cannula to a stirred solution of methyl 3-oxocyclobutane carboxylate (500 mg, 3.90 mmol) in dry Et20 (35 mL) at – 78 ¡ãC under N2. The reaction mixture was allowed to warm to room temperature and was stirred for 1 h. Satd aq. NH4C1 was added and the mixture was stirred until a clear solution resulted. This mixture was extracted with Et20 (3 x). The combined extracts were dried (MgS04) and concentrated in vacuo to give the crude product, which was purified by flash chromatography (Biotage Horizon, 40M, Si, -30 mL/min, 100percent hexanes for 260 mL, gradient to 40percent EtOAc in hexanes over 5184 mL) to afford methyl 3-(2-fluoro-4-methoxyphenyl)-3- hydroxycyclobutanecarboxylate (450 mg, 45 percent). NMR (500 MHz, CDC13): delta 7.32 (t, J= 8.9 Hz, 1 H); 6.69-6.63 (m, 2 H); 3.80 (s, 3 H); 3.74 (s, 3 H); 3.40 (s, 1 H); 3.03-2.93 (m, 2 H); 2.90-2.82 (m, 1 H); 2.67-2.61 (m, 2 H).

According to the analysis of related databases, 458-50-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MERCK SHARP & DOHME CORP.; LU, Zhijian; CHEN, Yi-Heng; SMITH, Cameron; LI, Hong; THOMPSON, Christopher, F.; SWEIS, Ramzi; SINCLAIR, Peter; KALLASHI, Florida; HUNT, Julianne; ADAMSON, Samantha, E.; DONG, Guizhen; ONDEYKA, Debra, L.; QIAN, Xiaoxia; SUN, Wanying; VACHAL, Petr; ZHAO, Kake; WO2012/58187; (2012); A1;,
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Reference of 103291-07-2, A common heterocyclic compound, 103291-07-2, name is 4-Bromo-1-fluoro-2-methoxybenzene, molecular formula is C7H6BrFO, 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.

Add sodium hydride (2.77 g, 60% w/w, 69.2 mmol) to a solution of 3-hydroxy- azetidine-1-carboxylic acid tert-butyl ester (10.9 g, 62.9 mmol) in dimethyl sulfoxide (100 mL). Stir the mixture for 30 min and then add 3-bromo-6-fluoroanisole (15.5 g, 75.5 mmol). Heat the mixture to 65 0C overnight. Cool the mixture to room temperature and then dilute the solution with saturated ammonium chloride and brine and extract with ethyl acetate. Wash the organics five times with brine, then dry over sodium sulfate and filter. Concentrate and purify via silica gel chromatography using a 0-45% gradient of ethyl acetate/hexane to give 10.4 g (46%) of the title compound as a clear oil.

The synthetic route of 103291-07-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ELI LILLY AND COMPANY; WO2008/76562; (2008); A1;,
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Application of 13070-45-6, 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 13070-45-6 as follows.

General procedure: (S)-C10-BridgePHOS (2.0mg, 2.4mol%) and Pd(OCOCF3)2 (0.8mg, 2mol%) were placed into an oven dried flask under a nitrogen atmosphere, and degassed fresh dry acetone (2mL) was added. The mixture was stirred at room temperature for 1h. Then acetone was removed under vacuum and a solvent system of CH2Cl2/TFE (1/1, 1mL) was added to the mixture to afford the catalyst solution. The substrate 1 (0.15mmol) and additive (1equiv) were placed in a reaction tube under nitrogen and the above catalyst solution was added to the tube. The mixture was then degassed and transferred to a stainless steel autoclave in a glove box. After exchanging the gas three times, the hydrogenation was carried out at 35C under 60bar H2. After several hours, the reaction mixture was concentrated under reduced pressure. After alkalization with saturated NaHCO3, the percentage conversion of product was determined by 1H NMR analysis of the crude product. The organic residue was purified by flash chromatography with ethyl acetate/petrol ether (1:50) to give pure product 2. Enantiomeric excess was determined using a Daicel Chiralcel column with hexane/i-propyl alcohol as the eluant.

According to the analysis of related databases, 13070-45-6, the application of this compound in the production field has become more and more popular.

Reference:
Article; Li, Chao; Chen, Jianzhong; Fu, Guanghong; Liu, Delong; Liu, Yangang; Zhang, Wanbin; Tetrahedron; vol. 69; 33; (2013); p. 6839 – 6844;,
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Some common heterocyclic compound, 53087-13-1, name is 1-(Benzyloxy)-3-bromobenzene, molecular formula is C13H11BrO, 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: C13H11BrO

.2 eq BuLi in hexane,1.2 eq TMEDA, 8 eq SO2 in Et2O, 3 eq N-chlorosuccinimide, EtjO, -75 C to 25 C, then dioxane, aq NH3. 250C1 16 hA solution of l-benzyloxy-3-bromobenzene (28.3 g) in Et2O (375 mL) is cooled to – 70 C and treated with TMEDA (19.2 mL) and tt-BuLi in hexane (1.6 M, 79 mL). The solution is stirred at -70 C for 1 h and transferred into a cooled solution (-70 0C) of SO2 (54.4 g) in Et2O (375 mL). The mixture is kept at -700C for 15 minutes, then allowed to warm to RT over 1 h. The solvent is evaporated and the residue is suspended in aqueous sodium phosphate (IM, 750 mL, pH 6). EtOAc (500 mL) is added and the solution is cooled to 00C. JV-Chlorosuccinimide (43.5 g) is slowly added and the pH is readjusted to pH 6 by addition OfNa3PO4. The reaction mixture is stirred vigorously for 1 h. The phases are separated and the aqueous phase is extracted twice with EtOAc. The combined organic phases are washed with H2O and brine, dried and concentrated to give a yellowish oil. The residue is taken up in dioxane (400 mL) and NH3 in H2O (28%, 200 mL) is added. The reaction mixture is stirred for 12 h and then concentrated to dryness. The residue is chromatographed on SiO2 gel (eluent hexanes/EtOAc 4:1 to 3:7) to give 3-benzyloxy- benzenesulfonamide as a white powder. API-MS: M-I ?= 262.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 53087-13-1, its application will become more common.

Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GmbH; WO2007/120595; (2007); A2;,
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Synthetic Route of 6358-77-6, The chemical industry reduces the impact on the environment during synthesis 6358-77-6, name is 5-Bromo-2-methoxyaniline, I believe this compound will play a more active role in future production and life.

Step 1: water (5 mL), boric acid (55 mg, 0.89 mmol) and glycerol (2-3 drops) were added to a stirred solution of 5-bromo-2-methoxyaniline (600 mg, 2.97 mmol) and divinylsulfone (351 mg, 2.97 mmol). The resulting mixture was stirred at reflux for 18h. The reaction mixture was cooled to rt and extracted withEtOAc. The organic layer was washed three times with water, dried over Mg504, filtered and the solution was evaporated under reduced pressure. Thecrude product was purified by silica gel column chromatography using Hexanes/EtOAc (50:50) as eluent yielding 4-(5-bromo-2-methoxyphenyl)-1- thiomorpholine-1,1-dione Ex.49a (900 mg, 95%). 1H NMR (400 MHz, DMSOd6, d in ppm): 3.22 (t, 4H, J=5.2Hz), 3.41-3.46 (m, 4H), 3.80 (s, 3H), 6.92-6.96(m, 1H), 7.12 (d, 1H, J=2.4Hz), 7.18 (dd, 1H, J=8.6Hz, J=2.4Hz).

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, 5-Bromo-2-methoxyaniline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GENFIT; DELHOMEL, Jean-Francois; PERSPICACE, Enrico; MAJD, Zouher; PARROCHE, Peggy; WALCZAK, Robert; BONNET, Pascal; FOGHA, Jade; (144 pag.)WO2018/138359; (2018); A1;,
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Electric Literature of 1462-37-9, 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. 1462-37-9, name is ((2-Bromoethoxy)methyl)benzene belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To a solution of methyl 2-cyanoacetate (0.885 ml, 10.09 mmol) in DMF (20.18 ml) at rt was added sodium hydride (0.969 g, 24.22 mmol), and the reaction mixture was stirred at rt for 15 min. tetrabutylammonium iodide (0.373 g, 1.009 mmol) and ((2-bromoethoxy)methyl)benzene (3.35 ml, 21.19 mmol) were added, and the reaction mixture was stirred at 90 ¡ãC for 3 h. Water was added and the aqueous layer was extracted with ether (x3). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and filtered, and the filltrate was evaporated in vacuo to give the crude product. The crude product was purified by silica gel chromatography eluting with 0-30percent ethyl acetate/hexanes to give methyl 4-(benzyloxy)-2-(2- (0187) (benzyloxy)ethyl)-2-cyanobutanoate (2.4 g, 6.53 mmol, 64.7 percent yield) as a colorless oil. NMR (500MHz, CHLOROFORM-d) delta 7.41 – 7.27 (m, 10H), 4.49 (s, 4H), 3.78 – 3.69 (m, 5H), 3.45 (s, 3H), 2.49 – 2.40 (m, 2H), 2.06 (dt, J=14.2, 4.7 Hz, 2H).

The synthetic route of ((2-Bromoethoxy)methyl)benzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; WU, Yong-Jin; GUERNON, Jason M.; (102 pag.)WO2018/81384; (2018); A1;,
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Synthetic Route of 22094-18-4, These common heterocyclic compound, 22094-18-4, name is 1,3-Dibromo-2,2-dimethoxypropane, 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.

Intermediate 314A: 1-(4-Bromophenyl)-3,3-dimethoxycyclobutanecarbonitrile To a suspension of NaH (0.733 g, 18.32 mmol, 60% in mineral oil) in DMF (14 mL) was added 2-(4-bromophenyl)acetonitrile (1.796 g, 9.16 mmol) followed by 1,3-dibromo-2,2-dimethoxypropane (2.0 g, 7.64 mmol) and the reaction mixture was heated to 60 C. and stirred for 12 h. The reaction mixture was cooled to RT, poured into water (150 mL) and extracted with EtOAc (3*40 mL). The combined organic layer was washed with brine, dried over Na2SO4, filtered and the filtrate concentrated. The crude product was purified by silica gel chromatography (24 g REDISEP column, eluting with 5% EtOAc in hexane). Fractions containing the product were combined and evaporated to afford Intermediate 314A as a white solid (2 g, 88%). 1H NMR (300 MHz, DMSO-d6) delta ppm 7.68-7.57 (m, 2H), 7.46-7.40 (m, 2H), 3.18 (s, 3H), 3.08 (s, 1H), 3.07 (s, 3H), 3.05-3.02 (m, 1H), 2.74-2.71 (m, 1H), 2.70-2.67 (m, 1H).

Statistics shows that 1,3-Dibromo-2,2-dimethoxypropane is playing an increasingly important role. we look forward to future research findings about 22094-18-4.

Reference:
Patent; Bristol-Myers Squibb Company; Velaparthi, Upender; Darne, Chetan Padmakar; Liu, Peiying; Wittman, Mark D.; Pearce, Bradley C.; Araujo, Erika M. V.; Dasgupta, Bireshwar; Nair, Jalathi Surendran; Janakiraman, Sakthi Kumaran; Rachamreddy, Chandrasekhar Reddy; Rao, Mettu Mallikarjuna; Karuppiah, Arul Mozhi Selvan Subbiah; Reddy, Bandreddy Subba; Nagalakshmi, Pulicharla; Bora, Rajesh Onkardas; Maheshwarappa, Shilpa Holehatti; Kumaravel, Selvakumar; Mullick, Dibakar; Sistla, Ramesh; (353 pag.)US9273058; (2016); B2;,
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