Category: 450-91-9

Some common heterocyclic compound, 450-91-9, name is 4-Fluoro-2-methoxyaniline, molecular formula is C7H8FNO, 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-Fluoro-2-methoxyaniline

Taking 200 ml 98 wt % sulfuric acid is added to a 500 ml three-port flask, ice water bath cooled to 5 – 10 C, then addition of 2 – methoxy -4 – fluoro aniline (41.0g, 0 . 29 muM), control of speed of addition, the reaction solution maintained at a temperature of 0 – 20 C; then adding KNO batch3(34.4g, 0 . 34 muM), keep the temperature of the reaction solution is 0 – 20 C, after adding the reaction liquid natural temperature to 25 C, reaction 2h end after. The reaction liquid slowly poured into the 1L the ice water, stirring after filtering out the solid, the filtrate 40 wt % NaOH to pH=9 and in, dropwise lye process is maintained in the temperature not higher than 40 C, after adding stirring 1h, separating solid, after the solid is filtered, washed with water solid to neutral, then dried to obtain the brown body solid 2 – methoxy -4 – fluoro -5 – nitroaniline 40.5g, yield is 75.2%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 450-91-9, its application will become more common.

Reference:
Patent; Shanghai University of Engineering Science; Sun, Mingchen; Mao, Yongjun; Zhang, Rui; Liu, Xiangyu; Wang, Han; (14 pag.)CN106366022; (2017); A;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Electric Literature of 450-91-9, These common heterocyclic compound, 450-91-9, name is 4-Fluoro-2-methoxyaniline, 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-Chloro-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid methyl ester (15.0 g), 4-fluoro-2-methoxyaniline (9.5 g), 4M hydrochloric acid in dioxane (4.5 ml) and dioxane (100.0 ml) were stirred at 100 C. overnight. Then the mixture was filtrated and the solid was dried in vacuo. Yield: 24.0 g ESI mass spectrum: m/z=348 (M+H)+

The synthetic route of 450-91-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; US2011/212103; (2011); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Application of 450-91-9, These common heterocyclic compound, 450-91-9, name is 4-Fluoro-2-methoxyaniline, 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.

To a solution of EDCI?HCl (573.2 mg, 2.99 mmol) in DMF (7 mL) and CH2Cl2 (7 mL) were successively added OxymaPure® (425.0 mg, 2.99 mmol) and S1 (1.00 g, 2.72 mmol) at room temperature. After stirring the reaction mixture for 5 min, 4-fluoro-2-methoxyaniline (470.6 mg, 2.99 mmol) dissolved in DMF (1 mL) and DIPEA (590 muL, 4.08 mmol) were added, the reaction mixture was stirred at the same temperature for 11 h. The volatiles were removed under reduced pressure. The residue was diluted with ethyl acetate and 1 N HCl aq. was added. The resulting mixture was extracted with ethyl acetate twice, the combined organic layers were washed with aqueous saturated NaHCO3 twice, H2O, brine and dried over Na2SO4. After filtration, the residue was concentrated under reduced pressure and dried in vacuo to give crude amide as brown solid. To the amide in DMF (9 mL) was added piperidine (240 muL, 4.08 mmol) and the reaction mixture was stirred at room temperature for 3 h. The reaction mixture was diluted with ethyl acetate and H2O was added. The resulting mixture was extracted with ethyl acetate twice, the combined organic layers were washed with H2O, brine, dried over Na2SO4. Filtrate was concentrated and the resulting residue was purified by silica gel chromatography (ethyl acetate/n-hexane = 12/88 to 100/0) to give S2 (464.9 mg, 1.73 mmol, 64percent over 2 steps) as a pale brown oil.Pale brown oil; [alpha]D27 ?6.1 (c 0.44, CH3OH); 1H NMR (400 MHz, CD3OD) delta 8.01 (dd, J = 8.8 , 6.2 Hz, 1H), 6.84 (dd, J = 10.5, 2.7 Hz, 1H), 6.66 (ddd, J = 8.8, 8.6, 2.7 Hz, 1H), 3.89 (s, 3H), 3.46 (dd, J = 7.3, 5.6 Hz, 1H), 1.86?1.77 (m, 1H), 1.66?1.53 (m, 2H), 1.35?1.29 (m, 2H), 0.93 (d, J = 6.6 Hz, 3H), 0.92 (d, J = 6.6 Hz, 3H); 13C NMR (100 MHz, CD3OD) delta 176.3, 161.4 (d, J = 240.6 Hz), 152.7 (d, J = 10.2 Hz), 124.3 (d, J = 3.6 Hz), 123.4 (d, J = 9.5 Hz), 107.1 (d, J = 21.9 Hz), 100.2 (d, J = 27.0 Hz), 56.9, 56.6, 35.8, 34.2, 29.2, 23.0, 22.9; 19F NMR (376 MHz, CD3OD) delta ?117.4; IR (neat) nu 3019, 2959, 1673, 1611, 1531, 1465, 1415, 1216, 757, 669 cm?1; HRMS (ESI) calcd. for C14H22N2O2F m/z 269.1660 [M+H]+, found 269.1651.

The synthetic route of 450-91-9 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Nonoyama, Akihito; Kumagai, Naoya; Shibasaki, Masakatsu; Tetrahedron; vol. 73; 11; (2017); p. 1517 – 1521;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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 450-91-9 as follows. Safety of 4-Fluoro-2-methoxyaniline

In a flask equipped with a water cooled condenser a phenyl amine (1.0 equiv.), bis(2- chloroethyl)amine hydrochloride (1.5 equiv.), potassium carbonate (1.5 equiv.) and sodium iodide (0.4 equiv.) were suspended in diglyme. The resulting reaction mixture was allowed to heat to reflux over a period of one hour and allowed to stir at reflux for an additional 2.5 hours. It was then partitioned between dichloromethane and distilled water. The pH of the water layer was adjusted to basic pH (9-10) with 5% aqueous sodium hydroxide. The water phase was extracted thrice with dichloromethane. The combined organic layers were washed once with 10% aqueous sodium thiosulfate to remove iodine, dried over anhydrous sodium sulfate and the solvent removed in vacuo. The product was purified by column chromatography in 2M ammonium/methanol and dichloromethane mixtures.; l-(4-Fluoro-2-methoxy-phenyl)-piperazine was synthesized from 4-Fluoro-2-methoxy- phenylamine (151.5 mg, 1.07 mmol), bis(2-chloroethyl)amine hydrochloride (287.4 mg, 1.61 mmol), potassium carbonate (222.5 mg, 1.61 mmol) and sodium iodide (64.5 mg, 0.43 mmol) in diglyme. Column chromatography 10% 2M ammonia/methanol in dichloromethane provided the product as a dark brown oil (89.8mg, 40%). 1H NMR (300 MHz, CDCl3): delta(ppm) 6.78-6.90(m, IH), 6.57-6.65(m, 2H), 3.86(s, 3H), 3.14(broad t, 2H), 3.05(broad t, 4H), 2.95(t, IH), 2.72(broad t, 2H).

According to the analysis of related databases, 450-91-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ASTRAZENECA AB; NPS PHARMACEUTICALS, INC.; WO2006/71730; (2006); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Reference of 450-91-9, The chemical industry reduces the impact on the environment during synthesis 450-91-9, name is 4-Fluoro-2-methoxyaniline, I believe this compound will play a more active role in future production and life.

Compound 2 (8.0 g, 43 mmol) was placed in a 500 ml one-necked reaction flask, and concentrated sulfuric acid (100 ml) was added to dissolve the substrate with constant agitation. At -20 C., concentrated nitric acid (6.15 ml, 48 mmol) was slowly added dropwise with stirring, and the reaction mixture was stirred for 5 mins at this temperature. The reaction progress was monitored by TLC. After the substrate was completely consumed, the mixture was poured into ice water. Sodium hydroxide/water solution (150 ml/300 ml) were added slowly to the reaction system which was kept in an ice-water bath at -20 C., and the pH of the mixture was adjusted to 8-9. After the neutralization, the reaction mixture was extracted with ethyl acetate/water system for three times, and the organic layer was separated, washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give compound a1 (8.7 g) which was used directly in the next reaction. Yield: 80%; purity: 100%; MS m/z(ESI): 187.0 [M+H]+; 1H NMR (400 MHz, DMSO-d6): delta 7.34 (d, J=7.8 Hz, 1H), 7.04 (d, J=13.4 Hz, 1H), 5.25 (brs, 2H), 3.90 (s, 3H).

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, 4-Fluoro-2-methoxyaniline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; SHANGHAI HAIYAN PHARMACEUTICAL TECHNOLOGY CO., LTD.; YANGTZE RIVER PHARMACEUTICAL GROUP CO., LTD.; LAN, Jiong; JIN, Yunzhou; ZHOU, Fusheng; HE, Qi; HE, Xiangyu; LV, Qiang; (87 pag.)US2017/57957; (2017); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Reference of 450-91-9, The chemical industry reduces the impact on the environment during synthesis 450-91-9, name is 4-Fluoro-2-methoxyaniline, I believe this compound will play a more active role in future production and life.

Ice bath,4-Fluoro-2-methoxyaniline (6.5 g, 46 mmol) was dissolved in concentrated sulfuric acid (50 mL)After stirring for 30 minutes in an ice bath,Potassium nitrate (5.2 g, 51 mmol) was added portionwise,After the addition, the reaction was allowed to proceed to room temperature and the reaction was stirred for 12 hours.After completion of the reaction,The reaction was poured into ice and the pH was adjusted to 8 with the addition of ammonia, Ethyl acetate (200 mL × 3), dried over anhydrous sodium sulfate,Concentrated, and purified by column chromatography (petroleum ether: ethyl acetate = 3: 1) to give the title compound (6.9 g, yield 80%).

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, 4-Fluoro-2-methoxyaniline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Shandong Xuanzhu Pharmaceutical Technology Co., Ltd; Wu, Yongqian; (68 pag.)CN105884695; (2016); A;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Related Products of 450-91-9, A common heterocyclic compound, 450-91-9, name is 4-Fluoro-2-methoxyaniline, molecular formula is C7H8FNO, 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.

iii: Intermediate 3 (1.0 eq) and cesium carbonate (2.0 eq) and corresponding phenylamine (1.2 eq) were added into a dry reaction flask. Dry DMF was used as reaction solvent, N2 was used to remove water vapor and oxygen. Then catalyst and ligand Pd(AcO)2 (0.1 eq) and Xantphos (0.1 eq) were added. The reaction mixture was transferred to a 60 C oil bath, 6~7 hours. After the reaction completed, the mixture was filtered and evaporated. Intermediate 4 was gained. The yield was 50%.

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; Rong, Juan; Feng, Zhan-Zhan; Shi, Yao-Jie; Ren, Jing; Xu, Ying; Wang, Ning-Yu; Xue, Qiang; Liu, Kun-Lin; Zhou, Shu-Yan; Wei, Wei; Yu, Luo-Ting; Bioorganic and Medicinal Chemistry Letters; vol. 29; 19; (2019);,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Some common heterocyclic compound, 450-91-9, name is 4-Fluoro-2-methoxyaniline, molecular formula is C7H8FNO, 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. Computed Properties of C7H8FNO

Compound a1-2 (8.0 g, 43 mmol) was placed in a 500 mL single-necked reaction flask and concentrated sulfuricacid (100 mL) was added under stirring at a constant rate to dissolve the substrate. Concentrated nitric acid (6.15 mL,48 mmol) was slowly added dropwise to the stirred reaction flask at -20 C and stirred at that temperature for 5 minutes.The progress of the reaction was checked by TLC. After the reaction of the substrate was complete, the reaction mixturewas poured into iced water. In -20 C ice bath, the aqueous solution of hydroxide/water (150 mL/300 mL) was slowly added to the reaction system and pH was adjusted to 8-9. After neutralization, the reaction solution was extracted threetimes with ethyl acetate/water system. The organic layer was separated, washed with water and then saturated brine,dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the compound 4-fluoro-2-methoxy-5-nitroaniline a1 (8.7 g) which was directly used in the next step. Yield: 80%; purity: 100%; MS m/z(ESI): 187.0 [M+H]+;1HNMR (400 MHz, DMSO-d6): delta 7.34 (d, J = 7.8 Hz, 1H), 7.04 (d, J = 13.4 Hz, 1H), 5.25 (brs, 2H), 3.90 (s, 3H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 450-91-9, its application will become more common.

Reference:
Patent; Shanghai Haiyan Pharmaceutical Technology Co., Ltd.; Yangtze River Pharmaceutical Group Co., Ltd.; LAN, Jiong; JIN, Yunzhou; ZHOU, Fusheng; LEI, Jing; WEN, Chong; ZHANG, Zhiyuan; HE, Xiangyu; (57 pag.)EP3173412; (2017); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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. 450-91-9, name is 4-Fluoro-2-methoxyaniline, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 450-91-9

In a dry round bottom flask acetic acid (950 ml) and 4-fluoro-2-methoxyaniline (380 gms) were added. The reaction mass was stirred at 25-30°C for 10-15 minutes. Acetic anhydride (439 gms) was added slowly to the reaction mass at 25- 35°C in 1.0-2.0 hrs. The reaction mass was heated to 90°C and stirred at same temperature for 3.0-5.0 hrs. The reaction mass was decomposed into water (1000 ml) and stirred at 25-30°C for 1.0-2.0 hrs. The solid was filtered and washed with water (300 ml). The reaction mass was extracted with ethyl acetate (2000 ml). Total organic layers were washed with NaHC03 solution (NaHC03 (100 gms) + water-4 (500 ml)) followed by washed with water (1000 ml), then washed with brine solution (NaCl (50 gms) + water-6(250 ml)) and dried over sodium sulphate (200 gms). The solvent was distilled out under vacuum. Petroleum ether (500 ml) was added to the residue and cooled to below 10°C and stirred for 30 minutes. The solid was filtered off and washed with petroleum ether (150 ml). The solid was dried at 50-60°C for 3-5 hrs (Yield – 410 gms; 83.13percent).

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 450-91-9.

Application of 450-91-9, 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. 450-91-9, name is 4-Fluoro-2-methoxyaniline belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

iii: Intermediate 3 (1.0 eq) and cesium carbonate (2.0 eq) and corresponding phenylamine (1.2 eq) were added into a dry reaction flask. Dry DMF was used as reaction solvent, N2 was used to remove water vapor and oxygen. Then catalyst and ligand Pd(AcO)2 (0.1 eq) and Xantphos (0.1 eq) were added. The reaction mixture was transferred to a 60 C oil bath, 6~7 hours. After the reaction completed, the mixture was filtered and evaporated. Intermediate 4 was gained. The yield was 50%.

The synthetic route of 4-Fluoro-2-methoxyaniline has been constantly updated, and we look forward to future research findings.