Category: 57946-56-2

57946-56-2, 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. 57946-56-2, name is 4-Chloro-2-fluoroaniline belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

EXAMPLE 5 Preparation of N-(4-chloro-2-fluorophenyl)-1-cyclohexene-1,2-dicarboximide A solution of 4-chloro-2-fluoroaniline (19.0 g, 130.6 mmol) and 3,4,5,6-tetrahydrophthalic anhydride (19.85 g, 130.6 mmol) in acetic acid is refluxed for 2 hours, treated with additional 4-chloro-2-fluoroaniline (3.0 g), refluxed for 90 minutes, stirred at room temperature overnight and poured into water. The resultant aqueous mixture is extracted with ethyl acetate. The organic extract is washed sequentially with water, saturated sodium hydrogen carbonate solution and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuoto obtain a purple oil. Flash column chromatography of the oil using silica gel and 15 to 20% ethyl acetate in hexanes solutions gives the title product as an off-white solid (25.3 g, 69% yield, mp 81-82C) which is identified by 1H, 13C and 19F NMR spectral analyses.

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

Reference:
Patent; American Cyanamid Company; EP985670; (2000); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Related Products of 57946-56-2,Some common heterocyclic compound, 57946-56-2, name is 4-Chloro-2-fluoroaniline, molecular formula is C6H5ClFN, 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 solution of 4-chloro-6-hydroxy-7-methoxyquinoline (3.0 g, 14 mmol) and 4-chloro-2-fluoroaniline (3.5 g, 23 mmol) in cyclohexanol (100 ml) containing 1M ethereal hydrogen chloride (16 ml) was heated at 155 C. for 18 hours.. After cooling the mixture was diluted with ether and isohexanes and the precipitate was collected by filtration.. The crude product was dissolved in a mixture of methylene chloride/methanol/ammonia (100/10/1) and silica (10 g) was added.. The solvent was removed by evaporation and the resulting powder was purified by flash chromatography eluding with methylene chloride/methanol/ammonia (95/5/1 increasing to 80/20/1) to give 4-(4-chloro-2-fluoroanilino)-6-hydroxy-7-methoxyquinoline (1.12 g, 25%). 1H NMR Spectrum: (DMSOd6) 3.95 (s, 3H); 6.30 (m, 1H); 7.25 (s, 1H);7.35 (m, 2H); 7.55 (m, 2H); 8.20 (d, 1H); MS (ESI): 319 [MH]+.

The synthetic route of 57946-56-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Zeneca Limited; Zeneca Pharma S.A.; US6809097; (2004); B1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Related Products of 57946-56-2, These common heterocyclic compound, 57946-56-2, name is 4-Chloro-2-fluoroaniline, 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.

The starting material was prepared as follows: A solution of 7-benzyloxy-4chloro-6-methoxyquinazoline (1.2 g, 4 mmol), (prepared as described for the starting material in Example 1), and 4-chloro-2-fluoroaniline (4441 mul, 4 mmol) in 2-propanol (40 ml) was refluxed for 1.5 hours. After cooling, the precipitate was collected by filtration, washed with 2-propanol then ether and dried under vacuum to give 7-benzyloxy-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (1.13 g, 64%). m.p. 239-242 C. 1H NMR Spectrum: (DMSOd6) 4.0(s, 3H); 5.36(s, 2H); 7.39-7.52(m, 9H); 8.1(s, 1H); 8.75(s, 1H); MS-ESI: 410 [MH]+; Elemental analysis: Found C, 59.2; H, 4.3; N, 9.4; C22H17N3O2ClF 1 HCl Requires C, 59.2; H, 4.1; N, 9.41%.

Statistics shows that 4-Chloro-2-fluoroaniline is playing an increasingly important role. we look forward to future research findings about 57946-56-2.

Reference:
Patent; Zeneca Limited; Zeneca Pharma S.A.; US6414148; (2002); B1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 57946-56-2,Some common heterocyclic compound, 57946-56-2, name is 4-Chloro-2-fluoroaniline, molecular formula is C6H5ClFN, 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 4-chloro-2-fluoroaniline (1.15 g, 7.9 mmol) in 125 mL of ethanol added silver sulphate (1.7 g, 8.3 mmol), then followed by addition of I2 (2.1 g, 8.3 mmol) in portions. After the addition was completed, the mixture was stirred at RT for 2 hours. The mixture was filtered through celite and the filtration was evaporated to give dark oil which was dissolved in 125 mL of DCM. The solution was washed with 2M sodium hydroxide (40 mL×2), saturated Na2S2O3 (40 mL×2) and water (40 mL×2). The resulting solution was dried over MgSO4 and then evaporated to give the crude 4-chloro-2-fluoro-6-iodoaniline as dark oil (2.1 g, yield: 98%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4-Chloro-2-fluoroaniline, its application will become more common.

Reference:
Patent; Hoffmann-La Roche Inc.; FENG, Song; GAO, LU; HONG, Di; WANG, Lisha; YUN, Hongying; ZHAO, Shu-Hai; (89 pag.)US2016/200741; (2016); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 57946-56-2, A common heterocyclic compound, 57946-56-2, name is 4-Chloro-2-fluoroaniline, molecular formula is C6H5ClFN, 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.

[0146] Sodium nitrite (2.35 g, 34.13mmol) solution (40 mL) was added dropwise to 4- Chloro-2-fluoro aniline (4. [5G,] 31mmol) in 170 mL HBr [AT-10C] bath temperature, then the mixture was stirred for 30 min at-10C bath temperature. In parallel, copper sulfate (10.22g, 24. [29MMOL)] and sodium bromide (3.79 g, 36. [8MMOL)] were mixed and the reaction mixture was heated at [60C] for 30 min. Then sodium sulfite (2.66g, 21. [2MMOL)] was added into this copper sulfate reaction mixture and heated for [95C] for 30 min. The reaction mixture was cooled to room temperature and solid formed was washed with water to afford white solid cuprous bromide. The diazonium salt was portion wise added into the freshly prepared cuprous bromide in 40 mL HBr [AT-10C] bath temperature and the reaction mixture was then warmed to room temperature. The reaction mixture was heated at [55C] for 20 min, cooled and then extracted with ethyl acetate three times. The combined organic layer was washed with water and saturated brine solution, dried over sodium sulfate and concentrated. The crude material was purified by column chromatography (5: 95 ethyl acetate: pet ether) to afford solid product.

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; CHEMOCENTRYX, INC.; WO2003/105853; (2003); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 57946-56-2, A common heterocyclic compound, 57946-56-2, name is 4-Chloro-2-fluoroaniline, molecular formula is C6H5ClFN, 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.

tert-Butyl 4- {[(4-CHLORO-6-METHOXYQUINAZOLIN-7-YL) OXY3METHYL} PIPERIDINE-1- carboxylate (L. OG, 2. 45MMOL), (prepared as described for the starting material in Example 1), and 4-chloro-2-fluoroaniline (0. 33ML, 2. 94MMOL) were stirred in 2-propanol (30ml) and hydrogen chloride (0. 74ML of a 4M solution in dioxane, 2. 94mmol) was added. The mixture was heated at reflux for 4 hours, cooled and filtered. The solid was dissolved in methanol, placed on an ISOLUTE0 SCX column, washed with methanol and then eluted with 7N ammonia in methanol to give 4- (4-CHLORO-2-FLUOROANILINO)-6-METHOXY-7- (PIPERIDIN-4- ylmethoxy) quinazoline (L. OG, 98%) as a white solid. LC-MS (ESI) 417.1 and 419. 1 [MH] + 1H NMR (spectrum): (DMSOd6) 1.47 (m, 2H); 1.93 (d, 2H); 2.13 (m, 1H); 2. 78 (t, 2H); 3.20 (d, 2H); 4.06 (m, 5H); 7.31 (s, 1H); 7.45 (m, 1H); 7.67 (m, 2H); 7.95 (s, 1H); 8.46 (s, 1H); 9.73 (br s, 1H)

The synthetic route of 57946-56-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2005/13998; (2005); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 57946-56-2, These common heterocyclic compound, 57946-56-2, name is 4-Chloro-2-fluoroaniline, 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.

A solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline (1.2 g, 4 mmol), (prepared for example as described in WO 00/47212 Example 1), and 4-chloro-2-fluoroaniline (444 [mu]l, 4 mmol) in 2-propanol (40 ml) was refluxed for 1.5 hours. After cooling, the precipitate was collected by filtration, washed with 2-propanol then ether and dried under vacuum to give 7-benzyloxy-4-(4-chloro-2-fluorophenylamino)-6-methoxyquinazoline hydrochloride (1.13 g, 64%). [0514] m.p. 239-242[deg.] C. [0515] <1>H NMR Spectrum: (DMSO-d6) 4.0 (s, 3H); 5.36 (s, 2H); 7.39-7.52 (m, 9H); 8.1 (s, 1H); 8.75 (s, 1H) [0516] MS-ESI: 410 [MH]<+>Elemental analysis:FoundC 59.2H 4.3N 9.4C22H17N3O2ClF 1 HClRequiresC 59.2H 4.1N 9.41%

The synthetic route of 57946-56-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Hennequin, Laurent Francois Andre; Stokes, Elaine Sophie Elizabeth; US2003/191308; (2003); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 57946-56-2, These common heterocyclic compound, 57946-56-2, name is 4-Chloro-2-fluoroaniline, 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 4-chloro-2-fluoroaniline (50.0 g, 344 mmol) in AcOH (3OmL) is added Ac2O (60 ml_) and the reaction is stirred at room temperature for 2 hours. The mixture is poured into ice water (500 mL) to give a solid precipitate. The mixture is stirred for an additional 1 hour at room temperature. The solid is filtered and washed with water and hexanes, then air dried to give lambda/-(4-chloro-2-fluorophenyl) acetamide

The synthetic route of 57946-56-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GmbH; WO2008/2853; (2008); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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 57946-56-2 as follows. Quality Control of 4-Chloro-2-fluoroaniline

A solution of 4-chloro-2-fluoroaniline (5.0 g, 34.3 mmol) in acetic acid (3 mL) was treated with acetic anhydride (6.45 mL, 68.7 mmol) and stirred at RT for 2 h. The mixture was poured onto ice water, stirred for 2 h and the resulting solid collected via filtration and dried to afford N-(4-chloro-2-fluorophenyl)acetamide (6.12 g, 95% yield). 1H NMR (400 MHz, DMSO-d6): delta 9.80 (s, 1H), 7.91 (t, J=8.7 Hz, 1H), 7.45 (dd, J=10.8, 2.4 Hz, 1H), 7.22 (d, J=8.9 Hz, 1H), 2.07 (s, 3H).

According to the analysis of related databases, 57946-56-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Deciphera Pharmaceuticals, LLC; Flynn, Daniel L.; Kaufman, Michael D.; Petillo, Peter A.; US8461179; (2013); B1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Related Products of 57946-56-2,Some common heterocyclic compound, 57946-56-2, name is 4-Chloro-2-fluoroaniline, molecular formula is C6H5ClFN, 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 solution of 4-chloro-6-hydroxy-7-methoxyquinoline (3.0 g, 14 mmol) and 4-chloro-2-fluoroaniline (3.5 g, 23 mmol) in cyclohexanol (100 ml) containing 1M ethereal hydrogen chloride (16 ml) was heated at 155 C. for 18 hours.. After cooling the mixture was diluted with ether and isohexanes and the precipitate was collected by filtration.. The crude product was dissolved in a mixture of methylene chloride/methanol/ammonia (100/10/1) and silica (10 g) was added.. The solvent was removed by evaporation and the resulting powder was purified by flash chromatography eluding with methylene chloride/methanol/ammonia (95/5/1 increasing to 80/20/1) to give 4-(4-chloro-2-fluoroanilino)-6-hydroxy-7-methoxyquinoline (1.12 g, 25%). 1H NMR Spectrum: (DMSOd6) 3.95 (s, 3H); 6.30 (m, 1H); 7.25 (s, 1H);7.35 (m, 2H); 7.55 (m, 2H); 8.20 (d, 1H); MS (ESI): 319 [MH]+.

The synthetic route of 57946-56-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Zeneca Limited; Zeneca Pharma S.A.; US6809097; (2004); B1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics