Month: July 2021

Electric Literature of 38336-04-8,Some common heterocyclic compound, 38336-04-8, name is 2-(Benzyloxy)-1-ethanamine, molecular formula is C9H13NO, 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.

To a solution of(2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-isothiocyanato-tetrahydro-2H-pyran-2,4,5-triyl triacetate (9.8 g, 25 mmol) in dichloromethane (100 mL) was added 128 (4 g, 26 mmol) at 0 C. After stirred for 2 hours, trifluoro acetic acid (15.4 g, 159 mmol) was added. The resulting solution was stirred for 12 hours at room temperature, then quenched with ice- water (200 mL) and neutralized by the addition ofNaHCC”3 (26 g, 318 mmol). The organic layer was separated and the aqueous layer was extracted with dichloromethane (3×100 mL). The combined organic layer was washed with brine (2×100 mL), dried over anhydrous sodium sulfate, and concentrated under vacuum to give a residue, which was purified by silica gel column, eluted with 10 % – 50 % ethyl acetate in petroleum ether to afford 129 as a white syrup (9.8 g, 77 %). (ES, m/z) [M+H]+ 481.0; 1H NMR (300 MHz, CDC13) delta 7.31 – 7.38 (m, 5H), 6.24 (d, / = 6.3 Hz, 1H), 5.41 – 5.43 (m, 1H), 4.94 – 4.98 (m, 1H), 4.55 (s, 2H), 4.34 – 4.37 (m, 1H), 4.14 – 4.16 (m, 3H), 3.83 – 3.87 (m, 1H), 3.64 (t, / = 5.4 Hz, 2H), 3.53 (t, / = 5.1 Hz, 2H), 2.12 (s, 3H), 2.10 (s, 3H), 2.09 (s, 3H).

The synthetic route of 38336-04-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ALECTOS THERAPEUTICS INC.; MERCK SHARP & DOHME CORP.; CHANG, Jiang; LIU, Kun; MCEACHERN, Ernest J.; MU, Changwei; SELNICK, Harold G.; SHI, Feng; VOCADLO, David J.; WANG, Yaode; WEI, Zhongyong; ZHOU, Yuanxi; ZHU, Yongbao; WO2012/62157; (2012); A1;,
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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. 767-91-9, name is 2′-Methoxyphenyl acetylene, A new synthetic method of this compound is introduced below., category: ethers-buliding-blocks

General procedure: To a mixture of alpha-azidoamide 16aa (34 mg, 0.20 mmol) and phenylacetylene (9a; 24 L,0.20 mmol) in t-BuOH/H2O (2 mL, 1:1) were added 0.5 M CuSO4 (0.020 mL, 0.010 mmol) and 1.0 M sodium ascorbate (0.020 mL, 0.020 mmol). The reaction mixture was stirred at room temperature for 1 day, and then the resulting reaction mixture was filtered. The separated solid was washed with H2O and hexanes, and triturated with hexane/EtOAc (10:1) to give the 1-morpholino-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanone (2aaa; 52 mg, 96%) as a white 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:
Article; Lee, Doohyun; Kim, Daehun; Lee, Seungyeon; Kim, Taegeum; Kim, Joobin; Kim, Sohee; Liu, Kwang-Hyeon; Lee, Sangkyu; Bae, Jong-Sup; Song, Kyung-Sik; Cho, Chang-Woo; Son, Youn Kyung; Baek, Dong Jae; Lee, Taeho; Molecules; vol. 20; 11; (2015); p. 19984 – 20013;,
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Reference of 7025-06-1, A common heterocyclic compound, 7025-06-1, name is 1-Bromo-2-phenoxybenzene, molecular formula is C12H9BrO, 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.

Preparation of intermediate C01-A: 1-bromodiphenyl ether (2.49 g, 0.01 mol) was dissolved in 100 mL of dry tetrahydrofuran under nitrogen atmosphere, when the internal temperature of the system was lowered to -75 C,Slowly add 4.8 mL of n-hexane solution of n-butyllithium (2.5 mol/L).After the completion of the dropwise addition, the reaction was kept at -75 C for 2 h, and the temperature was maintained.Add 9,9-dimethyl-5H,9H-quinoline[3,2,1-de]acridone solid(2.80g, 0.009 mol), add the insulation reaction for 2h, keep warm,The reaction was continued at room temperature for 2 h, after which 70 g of a 10% by mass dilute hydrochloric acid was added dropwise.Stir for 1 h, separate the liquid, collect the organic phase, remove the solvent, and obtain 5 g of oil;Further, 60 g of glacial acetic acid and 1.0 g of concentrated hydrochloric acid having a concentration of 36.5 wt% were added to the obtained oil.The temperature was raised to reflux, the reaction was kept for 5 hours, the temperature was lowered to 25 C, and 50 g of toluene and 100 g of water were added.The liquid phase is separated, the organic phase is desolvated, the crude oil is passed through a silica gel column, and the petroleum ether is rinsed. The column liquid containing a single product component is collected, and 50 g of petroleum ether is beaten after desolvation, and the filter cake is collected by suction filtration.Obtaining intermediate C01-A,White solid powder 2.52g,Yield 60.4%.

The synthetic route of 7025-06-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CECEP Wanrun Co., Ltd.; Gao Shukun; Zhang Jiangfeng; Sheng Lei; Li Peng; Ma Yongjie; Qin Yuhu; (20 pag.)CN109970775; (2019); A;,
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Electric Literature of 39021-83-5,Some common heterocyclic compound, 39021-83-5, name is 1,4-Dimethoxy-2,3-dimethylbenzene, molecular formula is C10H14O2, 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 2,3-Dimethyl-5,6-dinitro-1,4-dimethoxybenzene A solution of 2,3-dimethyl-1,4-dimethoxybenzene (16.6 g; o.1 mol) in acetic acid (100 mL) was cooled in an ice bath, then conc. HNO3 (40 mL) was added dropwise over 15 minutes. After the addition, the reaction mixture was stirred at ambient temperature for 3 hours, then heated at 50 C. for 20 minutes. Solution was concentrated to 75 mL under vacuum, then poured into ice-H2O (350 mL). The yellow precipitate (8.1 g) was collected. Recrystallization from EtOH gave 5.4 g (18.5% yield) of 2,3-dimethyl-5,6-dinitro-1,4-dimethoxybenzene as a yellow solid, m.p. 147-150 C.

The synthetic route of 39021-83-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Wyeth; US6444694; (2002); B1;,
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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. 6298-96-0, name is 1-(4-Methoxyphenyl)ethylamine belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Safety of 1-(4-Methoxyphenyl)ethylamine

A slurry of sodium triacetoxyborohydride (4.54 Kg, 21.4 mol.) in dichloromethane (22 Liters) is treated with 6,7-dihydro-8(5/-/)-quinolinone (1.8 Kg, 12.3 mol.) followed by (1S)-1-[4-(methyloxy)phenyl]ethanamine (1.8 Kg, 11.9 mol).) and the reaction was allowed to stirr vigorously at 22 0C for 24 hrs. The reaction is quenched with 1 N NaOH (aprox 27 Liters) to achieve pH 8 in the aqueous layer. The phases were separated and the organic phase was treated with 1N sodium hydroxide ( aprox 3.5 Liters) to achieve pH 11 in the aqueous layer. The phases again separated. The dichloromethane solution was then concentrated to minimum volume and treated with heptane (18 Liters). The volume again concentrated to aprox 9 Liters. Precipitation occurred upon cooling to 22 0C. The suspension was further cooled to 00C. and filtered. Solids were dried at ambient temperature under vacuum with nitrogen to give (8S)-N-{(1S)-1-[4-(methyloxy)phenyl]ethyl}-5,6,7,8-tetrahydro-8- quinolinamine. (2.18 Kg, 63%) 1H NMR (400 MHz, DMSO-D6) delta ppm 8.36 (m, 1 H) 7.44 (m, 1 H) 7.29 (m, 2 H) 7.15 (m, 1 H) 6.83 (m, 2 H) 4.00 (m, 1 H) 3.70 (s, 3 H) 3.59 – 3.64 (m, 1 H) 2.66 (m, 1 H) 2.64 (s, 1 H) 2.53 (s, 1 H) 1.76 (s, 1 H) 1.64 (s, 1 H) 1.50 (s, 1 H) 1.39 (s, 1 H) 1.24 (m, 3 H)

The synthetic route of 6298-96-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2007/87549; (2007); A2;,
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Related Products of 7664-66-6,Some common heterocyclic compound, 7664-66-6, name is 4-Isopropoxyaniline, molecular formula is C9H13NO, 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 4: 8-Hydroxy-2-(4-isopropoxy-phenyl)-2-aza-spiror4.51decan-l-one4-Isopropoxy-phenylamine (11.3 g) was added to a solution of 4-hydroxy-l-(2-methoxy- ethyl)-cyclohexanecarboxylic acid ethyl ester (11.5 g) in toluene (361 ml). The mixture was stirred for 10 minutes at RT. Then, dimethylaluminiumchloride (0.9 M in hexane, 99 ml) was added dropwise and the reaction mixture was heated to reflux for 4 h. The mixture was then cooled to 0C, water (50 ml) was added dropwise then AcOEt (300 ml). The mixture was stirred further 30 minutes, more AcOEt was added, the layers were then separated, the organic layer was dried over MgS04, filtered and the solvent was evaporated off . The crude product was triturated with diethyl ether/heptane to give the title compound as a mixture of cis/trans isomers as brown solid (14.3 g) which was used directly in the next step. MS (m/e): 304.190 [MH+].

The synthetic route of 7664-66-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HUNZIKER, Daniel; NEIDHART, Werner; WO2012/130679; (2012); A1;,
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Synthetic Route of 1535-75-7, The chemical industry reduces the impact on the environment during synthesis 1535-75-7, name is 2-(Trifluoromethoxy)aniline, I believe this compound will play a more active role in future production and life.

To a stirred solution of 2, 4-dichloro-5-methoxypyrimidine (5 g, 28.08 mmol) in tertiary butyl alcohol (35 mL) under argon atmosphere were added 2-(trifluoromethoxy) aniline (4 g, 22.47 mmol) and diisopropylethylamine (35 mL) at RT. The reaction mixture was stirred at 160 C for 48 h in a sealed tube. After completion of the reaction (monitored by TLC), the volatile components were removed in vacuo. The crude material was purified by silica gel column chromatography using 10% EtOAc:hexanes to afford 2-chloro-5-methoxy- N-(2-(trifluoromethoxy) phenyl) pyrimidin-4-amine (2 g, 22%) as a colorless syrup. ?H-NMR (CDC13, 400 MHz): oe 8.64 (d, 1H), 7.79 (s, 1H), 7.72 (br s, 1H), 7.38 (t, 1H), 7.30-7.27 (m, 1H), 7.10-7.07 (m, 1H), 4.00 (s, 3H); LC-MS: 320.3 (M+1); (column; X Select CSH C-18 (50 x 3.0 mm, 3.5 .im); RT 4.63 mm. 0.05% Aq TFA: ACN; 0.80 ml/min); TLC: 15% EtOAc:hexanes (Rf 0.3).

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-(Trifluoromethoxy)aniline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; FORUM PHARMACEUTICALS INC.; BURNETT, Duane, A.; BURSAVICH, Matthew, Gregory; MCRINER, Andrew, J.; WO2015/66696; (2015); A1;,
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Some common heterocyclic compound, 19056-40-7, name is 4-Bromo-3-methoxyaniline, molecular formula is C7H8BrNO, 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. Recommanded Product: 4-Bromo-3-methoxyaniline

POCl3 (5.07 ml, 54.4 mmol) was added to a mixture of 4-bromo-3-methoxyaniline (10 g, 49.5 mmol) and malonicacid (5.15 g, 49.5 mmol) with thorough mixing, and the solution was then heated to 105°C. After 5 min, the reactionbegan to bubble vigorously and eventually formed a hard foam, and heating was continued for 1 h. After cooling, water(200 mL) was added, and the mixture was stirred for 30 min. The solid was filtered off and washed with water. 2N NaOH(300 mL) was added to the solid, and stirring was continued overnight. The remaining solid was filtered off. EtOH (5 mL)was then added to the filtrate, and the basic layer was then acidified with concentrated HCl to pH 2. The resulting solidwas then filtered off and washed with water. The solid was then transferred to a flask, and the remaining water wasremoved by stripping off EtOH (200 mL x 2). The solid was then further dried under high vacuum for 15 h to yield 8.75g (66percent) of the title compound as an off-white solid. LRMS ESI+ (M+H)+ 270.2/272.2

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 19056-40-7, its application will become more common.

Reference:
Patent; Merck Sharp & Dohme Corp.; MSD Italia S.r.l.; MCCAULEY, John, A.; LIVERTON, Nigel, J.; HARPER, Steven; MCINTYRE, Charles, A.; RUDD, Michael, T.; (73 pag.)EP2268285; (2018); B1;,
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Electric Literature of 7252-83-7, A common heterocyclic compound, 7252-83-7, name is 2-Bromo-1,1-dimethoxyethane, molecular formula is C4H9BrO2, 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.

4-hydroxythiobenzamide (30.64 g, 0.20 mol) and 2-bromo-1,1-dimethoxyethane (31.00 g, 0.20 mol) were stirred in ethanol (600 mL) at room temperature.P-toluenesulfonic acid (34.44 g, 0.20 mol) was added to the reaction solution.Heat to 90C for 24 hours.After the reaction was completed, it was cooled to room temperature, the solvent was distilled off under reduced pressure, water (200 mL) was added, and the pH was adjusted to 8 with saturated sodium bicarbonate solution.Dichloromethane (200 mL x 3) was extracted and the organic phases were combined and concentrated by evaporation under reduced pressure to give a yellow solid (21.3 g, 60%).

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; SUNSHINE LAKE PHARMA CO., LTD.; ZHANG, YINGJUN; ZHANG, JIANCUN; WANG, XIAOJUN; LIN, RUNFENG; CAO, SHENGTIAN; WANG, ZHAOHE; LI, JING; (226 pag.)TWI607995; (2017); B;,
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Related Products of 22236-10-8, 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. 22236-10-8 name is 4-(Difluoromethoxy)aniline, 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.

To a solution of 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxylic acid (XLIX) (1 g, 3.08 mmol), 4-(difluoromethoxy)aniline (XLI) (0.420 mL, 3.38 mmol) and HATU (1.286 g, 3.38 mmol) in DMF (10 mL) was added DIPEA (1.343 mL, 7.69 mmol). The reaction mixture was stirred at 60 C. for 2 h. Water was then added to the reaction mixture and extracted with EtOAc. The organic layer was washed with water, saturated aqueous NaHCO3 and brine. The organic layer was dried, filtered and concentrated. The crude product was triturated in MeOH and the resulting solid filtered to give 5-bromo-N-(4-(difluoromethoxy)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxamide as a white solid (CXLIII) (1.26 g, 2.70 mmol, 88% yield). ESIMS found C20H18BrF2N3O3 m/z 466.1 (M+H).

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

Reference:
Patent; Samumed, LLC; KC, Sunil Kumar; Mak, Chi Ching; Mittapalli, Gopi Kumar; Hofilena, Brian Joseph; Eastman, Brian Walter; Cao, Jianguo; Chiruta, Chandramouli; Bollu, Venkataiah; (145 pag.)US2019/263821; (2019); A1;,
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