Category: 22236-10-8

Application 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.

Example 12; 2-ButyI-5-(4-chIorophenyl)-4-{[4-(difluoromethoxy)phenyl]amino}isothiazol-3(2H)-one 1,1-dioxide; 2-Butyl-4-chloro-5-(4-chlorophenyl)isothiazol-3(2H)-one 1,1-dioxide (0.2Og, 0.60mmol) and 4-(difiuoromethoxy)-aniline (0.19Og, 1.20mmol) were mixed in MeCN (2.5mL). The mixture was heated in a microwave reactor at 130 C for 15 mins, then additional 60 mins and then at 140 0C for 15 mins, then additional 30 mins. The mixture was evaporated and the residue was purified by column chromatography (ISOLUTE SI 20 g/70 mL), eluting with heptane, then DCM:heptane (25:75, then 50:50), to give the title compound (0.122g, 45%);

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; ASTRAZENECA AB; WO2006/73363; (2006); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

22236-10-8, name is 4-(Difluoromethoxy)aniline, belongs to ethers-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. Safety of 4-(Difluoromethoxy)aniline

The nitro ether (149 mmol) was dissolved in ethanol (37.5 mL), diluted with water (25 mL), and was treated with ammonium chloride (84.7 mmol) and iron powder (105 mmol). The reaction mixture was heated at reflux for 30 minutes and the suspension was filtered through Celite. The filter cake was washed with ethanol three times and the combined filtrates were concentrated. The residue was dissolved in water and the pH adjusted to 9-10 with 5 M sodium hydroxide. The aqueous layer was extracted with ethyl acetate (3×100 mL) and the combined organic layers were dried (magnesium sulfate) and concentrated to a yellow oil. The oil was dissolved in acetic anhydride (23.5 mmol) and the reaction mixture was maintained at rt for 16 h. The reaction mixture was diluted with water (50 mL) and was neutralized with solid sodium bicarbonate. The precipitated solids were isolated by filtration, washed with water, and dried to provide the acetamide in 62% yield as a light yellow solid.

The synthetic route of 22236-10-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Xie, Wenge; Herbert, Brian; Ma, Jianguo; Nguyen, Truc Minh; Schumacher, Richard; Gauss, Carla Maria; Tehim, Ashok; US2005/250808; (2005); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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. 22236-10-8, name is 4-(Difluoromethoxy)aniline, A new synthetic method of this compound is introduced below., SDS of cas: 22236-10-8

Preparation 9 6-Chloro-N*4*-(4-difluoromethoxyphenyl)-2-methylpyrimidine-4,5-diamine; 4,6-dichloro-2-methyl-pyrimidin-5-ylamine (20.0 g, 110 MoI) was added with stirring to EtOH (80 mL) over 3 minutes to give complete solution. 4-Difluoromethyoxyaniline (18.8 g, 118 MoI) was then added with stirring over 3 minutes. A dark brown solution was observed. EtOH (20 mL) was then added followed by a premixed solution of c.HCI (10 mL) in EtOH (40 mL) at a steady rate over 20 minutes. A slight exotherm up to approx 2O0C was noted. The solution was then warmed to 850C and held at that temperature for 4 hours. The reaction mixture was then cooled to room temperature, and a beige solid precipitated. This reaction mixture was filtered then washed with EtOH (100 ml_) followed by MTBE (3OmL) to remove EtOH traces. The resultant solid was dried in vacuo over the weekend to give the title compound, as the hydrochloride salt, as a beige solid (17.2 g, 45%) 1H NMR (400MHz, CD3OD) delta = 2.55 (s, 3H), 6.89 (t, 1 H), 7.27 (d, 2H), 7.75 (d, 2H) LCMS (System 4) 3.07 mins; m/z (APCI) = 301 [MH+]

The synthetic route of 22236-10-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PFIZER LIMITED; WO2009/144632; (2009); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Electric Literature of 22236-10-8,Some common heterocyclic compound, 22236-10-8, name is 4-(Difluoromethoxy)aniline, molecular formula is C7H7F2NO, 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 31; 2-ButyI-5-(3-chlorophenyl)-4-{[4-(difluoromethoxy)phenyl]amino}isothiazol-3(2H)-one 1,1-dioxide; 2-Butyl-4-chloro-5-(3-chlorophenyl)isothiazol-3(2H)-one 1,1-dioxide (0.25Og, 0.75mmol) and 4-(difluoromethoxy)aniline (0.238g, 1.50mmol) were mixed in MeCN (2mL) and heated in a microwave reactor at 160C for 60 mins. The reaction mixture was evaporated and the residue was purified on a Horizon TM flash system using Heptane and EetOAc as eluant giving the title compound (0.25g, 72.9%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4-(Difluoromethoxy)aniline, its application will become more common.

Reference:
Patent; ASTRAZENECA AB; WO2006/73363; (2006); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Reference of 22236-10-8,Some common heterocyclic compound, 22236-10-8, name is 4-(Difluoromethoxy)aniline, molecular formula is C7H7F2NO, 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.

6-Benzyl-4-chloro-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (1.09 g, 4.21 mmol) prepared as described above (Intermediate 2, 1.0 g, 3.86mmol) was dissolved in anhydrous acetonitrile (3 mL) and 4-difluoromethoxyaniline was added (1.34 g, 8.42 mmol). The mixture was heated at 180 C. for 600 s in a microwave (Emrys Optimizer model, Personal Chemistry). The solvents were removed under vacuum to give the desired product as a beige powder (1.3 g, 94.2%). The crude product was used for the subsequent step.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4-(Difluoromethoxy)aniline, its application will become more common.

Reference:
Patent; Kelly, Michael G.; Kincaid, John; Kaub, Carl J.; US2006/258689; (2006); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Application of 22236-10-8, 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. 22236-10-8, name is 4-(Difluoromethoxy)aniline belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Example 6 N-(4-(difluoromethoxy)phenyl)-2-(imidazo[1,2-a]pyridin-5-yl)acetamide (0278) To a mixture of 2-(imidazo[1,2-a]pyridin-5-yl)acetic acid (50 mg) and anhydrous DMF (1.9 mL) were added 4-(difluoromethoxy)aniline (54 mg), HATU (160 mg) and DIPEA (0.059 mL) at room temperature, and the mixture was stirred at room temperature for 17 hr. To the reaction mixture were added water, saturated brine and saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (NH, ethyl acetate/methanol) and recrystallized from ethanol-hexane to give the title compound (31 mg). 1H NMR (300 MHz, DMSO-d6) delta4.14 (2H, s), 6.84-7.41 (5H, m), 7.54 (1H, d, J = 9.0 Hz), 7.58-7.66 (3H, m), 7.87 (1H, s), 10.50 (1H, s).

The synthetic route of 4-(Difluoromethoxy)aniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Takeda Pharmaceutical Company Limited; KIMURA, Eiji; MIYANOHANA, Yuhei; OGINO, Masaki; TANAKA, Yuta; FUSHIMI, Makoto; OKAWA, Tomohiro; HANYA, Yuki; KOIKE, Tatsuki; (67 pag.)EP3239150; (2017); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Adding a certain compound to certain chemical reactions, such as: 22236-10-8, name is 4-(Difluoromethoxy)aniline, 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 22236-10-8, Quality Control of 4-(Difluoromethoxy)aniline

General procedure: Step-1:4-amino-2,6-dichloro pyrimidine: 2,4,6-trichloro pyrimidine (1.0 mmol) in ethanol (5 mL) was treated with an aromatic amine (1.1 mmol) in the presence of Na2CO3 (1.1 mmol) at rt. The mixture was stirred at reflux for 2-4 h until completion of the reaction. The reaction progress was followed by TLC. After completion of the reaction, an equal volume of water was added with cooling. The resulting white precipitate was filtered, washed with water, and dried in vacuum over night to yield 4-substituted 2,6-dichloro pyrimidine. In case of no precipitation, ethanol was removed by rota vap., and the residue was dissolved in CH2Cl2. The organic layer was washed twice with water, brine, dried (Na2SO4), filtered, and concentrated. The resulting crude was purified by column chromatography to afford the 4-amino-2,6-dichloro pyrimidines in 85-95% yield. Step-2: 2,4-diamino-6-chloropyrimidine: 4-amino-2,6-dichloro pyrimidine (1.0 mmol) prepared from the above procedure was treated with another aliphatic amine or aromatic amine (2.0 mmol) in the presence of DIEPA (5.0 mmol) in n-BuOH (5 mL) at rt. For an aliphatic amine the reaction mixture was stirred at rt for overnight. For an aromatic amine the reaction mixture was refluxed for 24-72 h or placed in microwave (150 C, 2-7 h) until completion of the reaction. The reaction progress was followed by TLC. After completion of the reaction, solvents were removed by rota vap., and the residue was dissolved in CH2Cl2. The organic layer was washed twice with water, brine, dried (Na2SO4), filtered, and concentrated. The resulting crude was purified by column chromatography (EtOAc/hexane) to afford the 2,4-diammino-6-chloropyrimidines in 85-90% yield. Step-3: 2,4,6-triaminopyrimidine: 2,4-diamino-6-chloropyrimidine (1.0 mmol) prepared from the above procedure was treated with another suitable aliphatic amine or aromatic amine (3.0 mmol). For an aliphatic amine, 2,4-diamino-6-chloropyrimidine (1.0 mmol) was treated with aliphatic amine (3.0 mmol) and DIPEA (5.0 mmol) in n-BuOH (5 mL) and placed in microwave (150 C) for 3-7 h. After the completion of the reaction (monitored by TLC), solvents were removed and the residue was dissolved in EtOAc. The organic layer was washed twice with water, brine, dried (Na2SO4), filtered, and concentrated. The resulting crude was purified by column chromatography to afford the 2,4,6-triaminopyrimidines 90-95% yield. For aromatic amine; 2,4-diamino-6-chloropyrimidine (1.0 equiv) was dissolved in dioxane under argon and to that were added Pd2(dba)3 (10 mol %), Xantphos (10 mol %), aromatic amine (1.2 mmol), t-BuOK (1.2 mmol). The resulting solution was degassed with argon for 5 min and heated to 85 C for overnight. The reaction mixture was filtered through a pad of celite, washed with CH2Cl2 (2 × 10 mL) and the resulting filtrate was concentrated. The resulting crude was purified by flash column chromatography to yield 2,4,6-triaminopyrimidines in 90-95% yield.

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

Reference:
Article; Sagi, Vasudeva Naidu; Liu, Tianyu; Lu, Xiaoying; Bartfai, Tamas; Roberts, Edward; Bioorganic and Medicinal Chemistry Letters; vol. 21; 23; (2011); p. 7210 – 7215;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Adding a certain compound to certain chemical reactions, such as: 22236-10-8, name is 4-(Difluoromethoxy)aniline, 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 22236-10-8, Formula: C7H7F2NO

Example 2 3- { [4- (DIFLUOROMETHOXY) PHENYL] AMINO}-1- (2-METHOXYETHYL)-4-PHENYL-LH-PYRROLE-2, 5- dione 3-CHLORO-1-(2-METHOXYETHYL)-4-PHENYL-LH-PYRROLE-2, 5-dione (0.13 mmol, 36 mg) AND 4- difluoromethoxyaniline (0.28 mmol, 45 mg) were dissolved in DMF (1 mL). The mixture was heated in a microwave reactor at 150C for 20 min.. After cooling, the reaction mixture was purified by HPLC (95% 0. 1M ammonium acetate buffer: 5% CH3CN No. 100% CH3CN) to give 13 mg (24%) of the title COMPOUND. 1H NMR (400 MHz, CDC13) : 8 7.25 (bs, 1H), 7.19-7. 08 (m, 3H), 7.02-6. 97 (m, 2H), 6.81-6. 75 (m, 2H), 6.66-6. 60 (m, 2H), 6.36 (t, J=74.0 Hz, 1H), 3. 83 (t, J=5.7 Hz, 2H), 3.63 (t, J=5.7 Hz, 2H), 3. 38 (s, 3H)

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; ASTRAZENECA AB; WO2005/5417; (2005); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Adding a certain compound to certain chemical reactions, such as: 22236-10-8, name is 4-(Difluoromethoxy)aniline, 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 22236-10-8, COA of Formula: C7H7F2NO

5.1 Methyl 4-({[2-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-1-(2-chlorobenzyl)-4-iodo-1H-imidazol-5-yl]carbonyl}amino)benzoate (5t) To a solution of 4 (56.08 g, 100 mmol) in CH2Cl2 (1.3 L) were added (COCl)2 (16.5 g, 130 mmol) and DMF (5 ml) at 0 C. The reaction mixture was stirred at room temperature for 4 h and concentrated under reduced pressure. The residue was azeotroped with toluene and redissolved in toluene (1.3 L). To this solution was added DIPEA (38.8 g, 300 mmol) followed by methyl 4-aminobenzoate (19.7 g, 130 mmol). The reaction mixture was stirred at room temperature for 12 h. The reaction mixture was then quenched with saturated NH4Cl aqueous solution, extracted with EtOAc, washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica-gel column chromatography to give 5t (54.63 g, yield 79%) as a white amorphous. 1H NMR (300 MHz, CDCl3) delta 8.30 (br s, 1H), 8.01 (d, J = 8.7 Hz, 2H), 7.62 (d, J = 8.7 Hz, 2H), 7.39-7.36 (m, 1H), 7.22-7.13 (m, 2H), 6.82-6.78 (m, 1H), 5.58 (d, J = 16.2 Hz, 1H), 5.50 (d, J = 16.2 Hz, 1H), 4.93-4.90 (m, 1H), 3.90 (s, 3H), 3.77 (br s, 1H), 3.31 (dd, J = 3.3, 12.0 Hz, 1H), 2.93-2.84 (m, 3H), 1.78-1.54 (m, 4H), 1.49 (s, 9H); HRMS (ESI) [M+H]+ calcd for C29H34O5N5ClI 694.1288, found 694.1272; IR (ATR): 1714, 1675, 1591, 1513, 1434, 1405, 1311, 1280, 1243, 1222, 1172, 1110, 1060 cm-1; Anal. calcd for C29H33O5N5ClI: C, 50.19; H, 4.79; N, 10.09, found: C, 50.52; H, 4.95; N, 9.92.

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:
Article; Ikuma, Yohei; Hochigai, Hitoshi; Kimura, Hidenori; Nunami, Noriko; Kobayashi, Tomonori; Uchiyama, Katsuya; Furuta, Yudai; Sakai, Mutsuko; Horiguchi, Masakuni; Masui, Yumi; Okazaki, Kazuhiko; Sato, Yasuhiro; Nakahira, Hiroyuki; Bioorganic and Medicinal Chemistry; vol. 20; 19; (2012); p. 5864 – 5883;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Some common heterocyclic compound, 22236-10-8, name is 4-(Difluoromethoxy)aniline, molecular formula is C7H7F2NO, 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. Quality Control of 4-(Difluoromethoxy)aniline

General procedure: Step-1:4-amino-2,6-dichloro pyrimidine: 2,4,6-trichloro pyrimidine (1.0 mmol) in ethanol (5 mL) was treated with an aromatic amine (1.1 mmol) in the presence of Na2CO3 (1.1 mmol) at rt. The mixture was stirred at reflux for 2-4 h until completion of the reaction. The reaction progress was followed by TLC. After completion of the reaction, an equal volume of water was added with cooling. The resulting white precipitate was filtered, washed with water, and dried in vacuum over night to yield 4-substituted 2,6-dichloro pyrimidine. In case of no precipitation, ethanol was removed by rota vap., and the residue was dissolved in CH2Cl2. The organic layer was washed twice with water, brine, dried (Na2SO4), filtered, and concentrated. The resulting crude was purified by column chromatography to afford the 4-amino-2,6-dichloro pyrimidines in 85-95% yield. Step-2: 2,4-diamino-6-chloropyrimidine: 4-amino-2,6-dichloro pyrimidine (1.0 mmol) prepared from the above procedure was treated with another aliphatic amine or aromatic amine (2.0 mmol) in the presence of DIEPA (5.0 mmol) in n-BuOH (5 mL) at rt. For an aliphatic amine the reaction mixture was stirred at rt for overnight. For an aromatic amine the reaction mixture was refluxed for 24-72 h or placed in microwave (150 C, 2-7 h) until completion of the reaction. The reaction progress was followed by TLC. After completion of the reaction, solvents were removed by rota vap., and the residue was dissolved in CH2Cl2. The organic layer was washed twice with water, brine, dried (Na2SO4), filtered, and concentrated. The resulting crude was purified by column chromatography (EtOAc/hexane) to afford the 2,4-diammino-6-chloropyrimidines in 85-90% yield. Step-3: 2,4,6-triaminopyrimidine: 2,4-diamino-6-chloropyrimidine (1.0 mmol) prepared from the above procedure was treated with another suitable aliphatic amine or aromatic amine (3.0 mmol). For an aliphatic amine, 2,4-diamino-6-chloropyrimidine (1.0 mmol) was treated with aliphatic amine (3.0 mmol) and DIPEA (5.0 mmol) in n-BuOH (5 mL) and placed in microwave (150 C) for 3-7 h. After the completion of the reaction (monitored by TLC), solvents were removed and the residue was dissolved in EtOAc. The organic layer was washed twice with water, brine, dried (Na2SO4), filtered, and concentrated. The resulting crude was purified by column chromatography to afford the 2,4,6-triaminopyrimidines 90-95% yield. For aromatic amine; 2,4-diamino-6-chloropyrimidine (1.0 equiv) was dissolved in dioxane under argon and to that were added Pd2(dba)3 (10 mol %), Xantphos (10 mol %), aromatic amine (1.2 mmol), t-BuOK (1.2 mmol). The resulting solution was degassed with argon for 5 min and heated to 85 C for overnight. The reaction mixture was filtered through a pad of celite, washed with CH2Cl2 (2 × 10 mL) and the resulting filtrate was concentrated. The resulting crude was purified by flash column chromatography to yield 2,4,6-triaminopyrimidines in 90-95% yield.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 22236-10-8, its application will become more common.

Reference:
Article; Sagi, Vasudeva Naidu; Liu, Tianyu; Lu, Xiaoying; Bartfai, Tamas; Roberts, Edward; Bioorganic and Medicinal Chemistry Letters; vol. 21; 23; (2011); p. 7210 – 7215;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem