Category: 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. 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;,
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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.

Step 1 To a solution of cis-4-hydroxycyclohexane carbonic acid 6 (6.14 g, 42.6 mmol) in N,N’-dimethylformamide (40 mL) were added 4-difluoromethoxyaniline 7 (5.12 g, 35.5 mmol), HOBt (691 mg, 5.11 mmol) and EDC hydrochloride (9.77 g, 51.1 mmol) at room temperature, and the mixture was stirred overnight at room temperature. The reaction solution was poured into 1N hydrochloric acid and extracted with ethyl acetate, and then the organic layer was washed with saturated aqueous sodium bicarbonate and dried over magnesium sulfate, and then a solvent was removed in vacuo. The residue was washed with diethyl ether to yield the desired amide compound 8 (7.10 g, yield 70%) as a colorless solid.

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

Reference:
Patent; SHIONOGI & CO., LTD.; US2012/4227; (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. 22236-10-8, name is 4-(Difluoromethoxy)aniline, A new synthetic method of this compound is introduced below., name: 4-(Difluoromethoxy)aniline

In tetrahydrofuran (10 ml) was dissolved 4-difluoromethoxyaniline (1 .0 g 6.29 mmol). To this, pyridine (1 .0 ml, 12.58 mmol) and methane sulfonyl chloride (0.7 ml, 9.43 mmol) were added at 0-5 C and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate, washed with water and brine solution. Organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude product (1 .5 g) was used as such for next step. 1 H-NMR(400MHz,DMSO-d6)delta: 2.97(s,3H),7.16(d,J=8.8Hz,2H),7.16(t,J=7.4Hz, 1 H), 7.24 (d,J=9.2Hz,2H),9.77(s,1 H).

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

Reference:
Patent; DAIICHI SANKYO COMPANY, LIMITED; KATOCH, Rita; INAGAKI, Hiroaki; FUJISAWA, Tetsunori; WO2014/24056; (2014); A1;,
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Application 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.

A mixture of 2-[(fert-butyldimethylsilyloxy)methyl]-3-(4,6-dichloro-5- fluoropyrimidin-2-yl)-5-fluoropyrazolo[l,5-a]pyridine (102.0 mg, 0.23 mmol), 4- difluoromethoxy aniline (145.0 mg, 0.92 mmol) and ethanol (1 mL) was heated at 90C overnight. After cooling, the mixture was poured into ice- water to afford a solid. The solid was collected by filtration, followed by washing with water and hexane. The solid was dried under the vacuum to provide 2-[2-[(teri-butyldimethylsilyloxy)methyl]-5-fluoropyrazolo[l,5- a]pyridin-3-yl]-6-chloro-N-(4-difluoromethoxy)phenyl]-J-fluoropyrimidin-4-amine (a mixture of TBS protected and unprotected product).

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

Reference:
Patent; PTC THERAPEUTICS, INC.; LEE, Chang-Sun; BAIAZITOV, Ramil; CAO, Liangxian; DAVIS, Thomas, W.; DU, Wu; LIU, Ronggang; MOON, Young-choon; PAGET, Steven, D.; REN, Hongyu; SYDORENKO, Nadiya; WILDE, Richard, Gerald; WO2014/81906; (2014); A2;,
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Related Products of 22236-10-8, The chemical industry reduces the impact on the environment during synthesis 22236-10-8, name is 4-(Difluoromethoxy)aniline, I believe this compound will play a more active role in future production and life.

Step A: 6-(difluoromethoxy)benzo[d]thiazol-2-amine To 4-(difluoromethoxy)aniline (9.55 g, 60 mmol) in acetic acid (90 niL) was added potassium thiocyanate (KSCN) (12.41 mL, 240 mmol). The mixture was stirred for 20 minutes (KSCN dissolved into solution). To this mixture bromine (3.08 mL, 60.0 mmol) in acetic acid (40 mL) was added dropwise over 20 minutes. The reaction was stirred at room temperature overnight. It was poured into a mixture of 800 ml ice water and 200 ml saturated ammonium hydroxide. The product was extracted with ethyl acetate (5x). The organics were combined, washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford 6-(difluoromethoxy)benzo[d]thiazol-2-amine (12.6 g, 52.4 mmol, 87 % yield) as a yellow solid.

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:
Patent; BRISTOL-MYERS SQUIBB COMPANY; COOK II, James H.; MCDONALD, Ivar, M.; KING, Dalton; OLSON, Richard, E.; WANG, Nenghui; IWUAGWU, Christiana, I.; ZUSI, Christopher, F.; MACOR, John, E.; WO2011/53292; (2011); A1;,
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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.

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 (3xlOOmL) 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 4-(Difluoromethoxy)aniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MEMORY PHARMACEUTICALS CORPORATION; WO2005/63767; (2005); A2;,
Ether – Wikipedia,
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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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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. 22236-10-8, name is 4-(Difluoromethoxy)aniline, This compound has unique chemical properties. The synthetic route is as follows., Formula: C7H7F2NO

4-(Difluoromethoxy)aniline (1 g, 6.28 mmol) was dissolved in aqueous hydrochloric acid (12%, 7.35 ml, 25.1 mmol). The solution was cooled to 0 C. and sodium nitrite (434 mg, 6.28 mmol) dissolved in water (2 ml) was slowly added at a temperature below 5 C. After being stirred at 0 C. for 30 min, a solution of ethyl isocyanoacetate (711 mg, 6.28 mmol) and sodium acetate (5.16 g, 62.8 mmol) in MeOH (20 ml) and water (6 ml) was slowly added dropwise at the same temperature. The reaction mixture was stirred for 2 h at 0 C. The solvent was evaporated, 1 M hydrochloric acid was added and the mixture was extracted with ethyl acetate. The organic phase was washed with sodium bicarbonate solution and brine and dried with MgSO4. After chromatography (Silica gel, 40 g, 50% EtOAc in heptane) 220 mg ester was obtained that was dissolved in a mixture of tetrahydrofuran (2 ml), methanol (1 ml) and water (1 ml). Lithium hydroxide hydrate (97.8 mg, 2.33 mmol) was added and the solution was heated to 80 C. for 2 h. The solvent was removed under reduced pressure. The residue obtained was dissolved in 1 M hydrochloric acid and the solution was extracted with ethyl acetate twice. The combined organic layers were dried over MgSO4 and evaporated. The orange solid was recrystallized in a mixture of heptane and ethyl acetate (4:1). 121 mg (7%) of an off-white solid was obtained. 1H NMR (300 MHz, CDCl3) ? ppm: 7.34 (t, 1H; J=73 Hz), 7.41 (d, 2H; J=8.7 Hz), 7.95 (d, 2H; J=8.7 Hz), 9.38 (s, 1H).

According to the analysis of related databases, 22236-10-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Hoffmann-La Roche Inc.; Galley, Guido; Ghellamallah, Cedric; Norcross, Roger; Pflieger, Philippe; US2015/191458; (2015); A1;,
Ether – Wikipedia,
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Reference of 22236-10-8, These common heterocyclic compound, 22236-10-8, name is 4-(Difluoromethoxy)aniline, 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.

2-Butyl-4-{[4-(difluoromethoxy)phenyl]amino}-5-phenylisothiazol-3(2H)-one 1,1-dioxide; 2-Butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide (0.63g, 2.1mmol) and 4-(difluoromethoxy)-aniline (0.67g, 4.2mmol) were mixed in MeCN (4mL, dry). The mixture was put in a microwave reactor at 1600C for 1 hour, then for additional 1 hour then for 1 hour more. It was evaporated to dryness. The residue was purified by column chromatography (ISOLUTE SI, 50g/150mL), eluting with dichloromethane/heptane (50:50, then 75:25), to give the title compound (0.688g, 78%) as a yellow solid;

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

Reference:
Patent; ASTRAZENECA AB; WO2006/73364; (2006); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Synthetic Route 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