Month: February 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. 39021-83-5, name is 1,4-Dimethoxy-2,3-dimethylbenzene, A new synthetic method of this compound is introduced below., Safety of 1,4-Dimethoxy-2,3-dimethylbenzene

To a solution of 1,4-dimethoxy-2,3-dimethylbenzene (5 g, 30 mmol) in acetic acid (350 ml) was added bromine (1.54 ml, 30 mmol). After stirring for 10 min the mixture was quenched with aqueous bisulphate and extracted into ether (3¡Á50 ml). The organic layer was dried with magnesium sulfate and then the solvent removed under reduced pressure

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; Bedford, Robin B.; Bowen, John G.; Weeks, Amanda L.; Tetrahedron; vol. 69; 22; (2013); p. 4389 – 4394;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Synthetic Route of 104197-14-0, 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. 104197-14-0 name is 4-Bromo-2,6-difluoroanisole, 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.

[0241] Step a: Lithium diisopropylamine solution in THF (1 M, 25 mL, 25 mmol) was added slowly to a solution of 5-bromo-1,3-difluoro-2-methoxybenzene (4.5 g, 20.2 mmol) in anhydrous THF (50 mL) under N2 and vigorously stirred at 78 C. The reaction mixture was stirred at 60 C for 1 h, followed by rapid addition of DMF (5 mL). The reaction mixture was stirred at the same temperature and allowed to warm to 50 C over 1 h. The reaction was poured into a mixture of ice (200 g), concentrated hydrochloric acid (20 mL) and MTBE (100 mL) and the mixture was stirred and allowed to warm up to room temperature over 2 h. The oranic layer was separated, washed with brine and dried over MgSO4. The solvent was removed under reduced pressure to give 6-bromo-2,4-difluoro-3-methoxybenzaldehyde . MS: (ES) m/z calculated for C8H6BrF2O2 [M + H]+ 250.9, found 250.9.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Bromo-2,6-difluoroanisole, and friends who are interested can also refer to it.

Reference:
Patent; CHEMOCENTRYX, INC.; FAN, Pingchen; LANGE, Christopher W.; LUI, Rebecca M.; MALATHONG, Viengkham; MALI, Venkat Reddy; PUNNA, Sreenivas; SINGH, Rajinder; TANAKA, Hiroko; ZENG, Yibin; ZHANG, Penglie; (284 pag.)WO2018/222598; (2018); A1;,
Ether – Wikipedia,
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Reference of 651734-54-2, 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. 651734-54-2, name is 2,6-Difluoro-3,5-dimethoxyaniline belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To a stirred slurry of 2,6-difluoro-3,5-dimethoxyaniline (1.00 g, 5.29 mmol) in 6.0 M hydrogen chloride in water (9.00 mL, 54.0 mmol), a solution of sodium nitrite (0.383 g, 5.55 mmol) in water (2 mL) was added dropwise over 15 minutes at 0 C. After another 15 minutes, the resulting orange-red slurry was added to a solution of potassium iodide (3.50 g, 21.1 mmol) in water (5 mL) in small portions at 0 C. After addition, the reaction mixture was allowed to warm to room temperature and then it was stirred for 1 hout Solid precipitated which was filtered out. The solid was washed with water and dried under vacuum to give the desired product (1.15 g, 70%). 1H NMR (400 MHz, CDCl3): delta 6.68 (t, J=8.0 Hz, 1H), 3.88 (s, 6H) ppm.

The synthetic route of 2,6-Difluoro-3,5-dimethoxyaniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Incyte Corporation; Lu, Liang; He, Chunhong; Yao, Wenqing; US2014/45814; (2014); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Related Products of 53087-13-1, The chemical industry reduces the impact on the environment during synthesis 53087-13-1, name is 1-(Benzyloxy)-3-bromobenzene, I believe this compound will play a more active role in future production and life.

The (2S,4R)-4-(3-hydroxyphenyl)-4-methoxy-2-methyltetrahydropyran, used as a starting material, was obtained as follows: A Grignard reagent was prepared by heating a mixture of 3-benzyloxybromobenzene (4.2 g), magnesium (0.4 g), and tetrahydrofuran (10 ml) to reflux for 30 minutes. The mixture was allowed to cool to approximately 40 C. and a solution of (2S)-2-methyltetrahydropyran-4-one (1.55 g) in tetrahydrofuran (7 ml) was added dropwise. The mixture was stirred and warmed to 40 C. for 3 hours. The mixture was partitioned between ethyl acetate and cold dilute aqueous hydrochloric acid solution. The organic phase was washed with a saturated aqueous sodium chloride solution, dried (MgSO4) and evaporated. The residue was purified by column chromatography using a 10:3 v/v mixture of toluene and ethyl acetate as eluent. There was thus obtained, as a mixture of diastereoisomers, (2S,4R)- and (2S,4S)-4-(3-benzyloxyphenyl)-4-hydroxy-2-methyltetrahydropyran (3.71 g, 92%), as an oil, which was partly separated to give a fraction (2.33 g) which was enriched in the less polar diastereoisomer. Sodium hydride (55% w/w dispersion in mineral oil, 0.39 g) was added to a solution of the enriched fraction so obtained (2.33 g) in dimethylformamide (16 ml) which had been cooled to -5 C. and the mixture was stirred at this temperature for 1 hour. Methyl iodide (0.61 ml) was added and the mixture was stirred for 2 hours and allowed to warm to ambient temperature. The mixture was partitioned between ethyl acetate and ice-cold water. The organic phase was washed with a saturated aqueous sodium chloride solution, dried (MgSO4) and evaporated. The residue was purified by column chromatography using a 20:1 v/v mixture of toluene and ethyl acetate as eluent. There was thus obtained (2S,4R)-4-(3-benzyloxyphenyl)-4-methoxy-2-methyltetrahydropyran (1.99 g, 82%), as an oil. NMR Spectrum: (CDCl3, delta values) 1.2(d, 3H), 1.5-1.65(m, 1H), 1.9-2.05(m, 3H), 2.96(s, 3H), 3.8-4.0(m, 3H), 5.1(s, 2H), 6.85-7.05(m, 3H), 7.2-7.5(m, 6H).

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, 1-(Benzyloxy)-3-bromobenzene, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Imperial Chemical Industries PLC; ICI Pharma; US5134148; (1992); A;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Adding a certain compound to certain chemical reactions, such as: 1535-73-5, name is 3-Trifluoromethoxyaniline, 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 1535-73-5, COA of Formula: C7H6F3NO

Pentafluorophenyl chlorothionoformate (2.89 mL, 18.01 mmol) in DCM (10 mL) was added dropwise to 3-(Trifluoromethoxy)aniline (2.189 mL, 16.37 mmol) and Pyridine (1.986 mL, 24.56 mmol) in dichloromethane (180 mL) at O0C. The resulting solution was stirred at ambient temperature for 20 hours. The reaction mixture was washed sequentially with IM citric acid (100 mL), saturated NaHCCbeta (100 mL), and saturated brine (100 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 5 to 15percent ethyl acetate in isohexane. Pure fractions were evaporated to dryness to afford O- perfiuorophenyl 3-(trifluoromethoxy)phenylcarbamothioate (3.70 g, 56.0percent) as a yellow oil. IH NMR (400 MHz, CDC13) delta 7.08 (IH, s), 7.13 – 7.19 (2H, m), 7.38 (IH, t).

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2009/24821; (2009); A2;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Related Products of 5961-59-1, These common heterocyclic compound, 5961-59-1, name is 4-Methoxy-N-methylaniline, 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.

HATU (1.5 g, 4.0 mmol) was added to a stirred solution of 4-methoxy-N- methylaniline (500 mg, 3.64 mmol) and (S)-2-((tert-butoxycarbonyl)amino)-3-phenylpropanoic acid (1.06 g, 4.0 mmol) in DMF (20 mL) and DIPEA (1.3 mL, 7.3 mmol) and the reaction mixture was stirred at RT for 4h. The reaction was concentrated and the residual crude oil was partitioned between EtOAc (60 mL) and 1/2 sat. NaHCO3 (aq) (60 mL). The organic component was washed with brine (40 mL), dried (Mg504), filtered, concentrated and purified using a Biotage Horizon (80g5i02, 10-40% EtOAc/hexanes) to yield (5)-tert-butyl (1-((4- methoxyphenyl)(methyl)amino)- 1 -oxo-3 -phenylpropan-2-yl)carbamate (1.34 g) as a clear amber viscous oil. LC-MS retention time = 3.17 mm; mlz = 385.3 [M+H]. (Column: Phenonenex-Luna C18 2.0 x 50mm 3 pm. Solvent A = 95% Water:5% Acetonitrile:10 miVi NH4OAc. Solvent B = 5% Water:95% Acetonitrile:10 miViNH4QAc. Flow Rate = 0.8 mL/min. Start % B = 0. Final % B = 100. Gradient Time= 4 mm. Wavelength = 220). ?H NMR (400MHz, CDC13) oe 7.25 – 7.20 (m, 3H),7.03 – 6.64 (m, 6H), 5.20 (d, J=8.8 Hz, 1H), 4.53 (q, J=7.4 Hz, 1H), 3.83 (s, 3H),3.18 (s, 3H), 2.89 (dd, J=13.1, 7.5 Hz, 1H), 2.71 (dd, J=13.1, 6.5 Hz, 1H), 1.39 (s,9H).

The synthetic route of 5961-59-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; PENDRI, Annapurna; LI, Guo; BENDER, John A.; YANG, Zhong; WANG, Alan Xiangdong; BENO, Brett R.; FRIDELL, Robert A.; BELEMA, Makonen; MEANWELL, Nicholas A.; GENTLES, Robert G.; WO2015/61518; (2015); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Related Products of 52411-34-4,Some common heterocyclic compound, 52411-34-4, name is 1,2-Bis(o-aminophenoxy)ethane, molecular formula is C14H16N2O2, 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.

244kg 1,2-bis(o-aminophenoxy)ethane, 600kg mass percentage concentration of 30% hydrochloric acid and 1500kg water was stirred and beaten. Add 2000kg ice to cool to 5 deg.C. Add 363kg mass percentage concentration of 40% sodium nitrite to start diazotization. At diazotization end, eliminate excess sodium nitrite, to give a diazonium salt solution.280kg 5-aminoacetylacetylbenzimidazolone, dissolved in 250kg mass percentage concentration of 30% aqueous sodium hydroxide and 3000kg of water. Adjust the temperature to 5 deg.C. Add in a fine stream 1500 mass concentration of 10% diluted acetic acid until the acid precipitation end, pH value of 7, to obtain a coupling solution.The diazonium salt solution was slowly added over 3 hours to the coupling solution to undergo reaction. The pH during the coupling process was maintained using 850kg 30% concentration sodium bicarbonate to control the system pH to 7. The coupling ends. Temperature was raised to 90 deg. C, and maintained at this temperature for 2 hours, filtered to give the crude pigment filter cake. 1660kg solid content of 40% of the crude pigment filter cake was added to 4000kgDMF slurried in good stirring and heated to reflux, 5-8 hours of incubation, washing, drying at 85-90 deg.C under pulverized to obtain 665kg products.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1,2-Bis(o-aminophenoxy)ethane, its application will become more common.

Reference:
Patent; Shangyu?City Xinli Chemical Co.,Ltd.; Chen, Jianxin; Ni, Yuebiao; Zhang, Lixin; Fang, Biao; (15 pag.)CN105670340; (2016); A;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Electric Literature of 41365-75-7, These common heterocyclic compound, 41365-75-7, name is 1-Amino-3,3-diethoxypropane, 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.

Part A A solution of 1-amino-3,3-diethoxypropane (5.00 mL, 30.9 mmol) in 5 mL of tetrahydrofuran (THF) was treated with triethylamine (4.51 mL, 34.0 mmol) under an atmosphere of nitrogen and cooled to 0 C. The reaction mixture was then treated dropwise with a solution of di-tert-butyl dicarbonate (7.42 g, 34.0 mmol) in 25 mL of THF. The reaction mixture was stirred for 2 h at 0 C. and then allowed to come to room temperature. After 15 h, the reaction mixture was concentrated under reduced pressure, dissolved in ethyl acetate, washed with water (2*) and brine, dried over Na2SO4, filtered and concentrated under reduced pressure to yield tert-butyl (3,3-diethoxypropyl)carbamate (8.40 g) as a clear, faintly yellow oil.

The synthetic route of 41365-75-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Griesgraber, George W.; Manske, Karl J.; US2005/54640; (2005); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Electric Literature of 1535-75-7,Some common heterocyclic compound, 1535-75-7, name is 2-(Trifluoromethoxy)aniline, molecular formula is C7H6F3NO, 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 11(2 -Trifluoromethoxy-phenvD-hydrazine hydrochlorideTo a stirred solution of hydrochloric acid (37%, 1.6 L) at 0 0C is added 2- trifluoromethoxy-phenylamine (200 g, 113 mmol) followed by water (160 mL) and additional hydrochloric acid (160 mL). The mixture is warmed to room temperature, is stirred for 20 minutes, and is cooled to -5 0C. A solution of sodium nitrite (82 g, 1.19 mmol) in water (400 mL) is added dropwise keeping the internal temperature below 0 0C. The mixture is cooled to -5 0C and a solution of tin (II) chloride dihydrate (1020 g, 4520 mmol) in of HCl (37%, 3.2 L) is added dropwise keeping the internal temperature below O0C. The mixture is warmed to room temperature, is stirred for 3 h, filtered, and washed with 6 N HCl (3L) to obtain a yellow solid that is dried under vacuum overnight The title compound (115.8 g, 54%) is obtained pink-brown solid.Preparation 12 Trifluoromethoxy-phenyl-hydrazine hydrochlorideThe title compound (115.8 g, 54%) is prepared essentially according to the preparation of (2-trifluoromethoxy-phenyl)-hydrazine hydrochloride using 2- trifluoromethoxy-phenylamine.

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

Reference:
Patent; ELI LILLY AND COMPANY; WO2007/140183; (2007); A1;,
Ether – Wikipedia,
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Application of 321-28-8, These common heterocyclic compound, 321-28-8, name is 1-Fluoro-2-methoxybenzene, 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.

Step 1: 3-(3-fluoro-4-methoxybenzoyl)propionic acid Intermediate 351-Fluoro-2-methoxybenzene (7 mL, 0.062 mol) and succinic anhydride (6.93 g, 0.0692 mol) were dissolved in methylene chloride (100 mL). The resulting solution was cooled in an ice-water bath for 20 min. Aluminum trichloride (18.3 g, 0.137 mol) was then added in portions. Upon completion of addition, the mixture was heated at 65 C. in an oil bath for 2 h and then cooled to room temperature and allowed to stir overnight. The reaction mixture was poured onto ice and 200 mL 1N HCl was added. A white precipitate formed which was isolated by suction filtration. The filter cake was dried under suction and then further dried under vacuum to provide the title compound as a white solid (12.703 g, 90%). LC-MS: (FA) ES- 225; NMR (400 MHz, CD3OD) delta ppm 7.86 (ddd, J=8.6, 2.1, 1.14 Hz, 1H), 7.72 (dd, J=12.1, 2.1 Hz, 1H), 7.20 (dd, J=8.5, 8.5 Hz, 1H), 3.95 (s, 3H), 3.28-3.23 (m, 2H), 2.71-2.66 (m, 2H).

The synthetic route of 321-28-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Millennium Pharmaceuticals, Inc.; US2012/15942; (2012); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem