Category: 367-22-6

Synthetic Route of 367-22-6, 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. 367-22-6, name is 4-Chloro-3-fluoroaniline, This compound has unique chemical properties. The synthetic route is as follows.

4.1.1 Ethyl 2-((4-chloro-3-fluorophenyl)amino)-2-oxoacetate (6a) To a stirred solution of 3-fluoroaniline (1.11 g, 10.0 mmol) in CHCl3 (30.0 mL) was added dropwise N-chlorosuccinimide (NCS) in CHCl3 (20.0 mL) at 0 C. The mixture was stirred at 0 C for 42 h. After the reaction mixture was concentrated under reduced pressure, the residue was dissolved in Et2O. The mixture was washed with water, and dried over MgSO4. Concentration under reduced pressure followed by flash chromatography over silica gel with EtOAc/n-hexane gave 4-chloro-3-fluoroaniline (259.4 g, 18% yield) as crystalline solids. To a stirred solution of the above aniline (259.4 mg, 1.78 mmol) in THF (8.9 mL) were added at 0 C ethyl chloroglyoxylate (237.3 muL, 2.14 mmol) and Et3N (296.6 muL, 2.14 mmol). The mixture was stirred at room temperature for 12 h. After the precipitate was filtrated off, the filtrate solution was concentrated under reduced pressure. The residue was dissolved in EtOAc, and washed with 1.0 M HCl, saturated NaHCO3 and brine, then dried over MgSO4. Concentration under reduced pressure to provide the title compound 6a (435.2 mg, 99% yield) as brown crystals, which was used without further purification. 1H NMR (500 MHz, CDCl3) delta 1.44 (t, J = 7.50 Hz, 3H), 4.43 (q, J = 7.50 Hz, 2H), 7.24-7.25 (m, 1H), 7.35-7.40 (m, 1H), 7.70-7.75 (m, 1H), 8.93 (br, 1H); 13C NMR (125 MHz, CDCl3) delta 13.0, 64.1, 108.5 (d, J = 26.3 Hz), 115.9 (d, J = 3.75 Hz), 117.3 (d, J = 18.8 Hz), 130.9 (d, J = 10.0 Hz), 135.9, 153.9, 158.1 (d, J = 246.3 Hz), 160.5; HRMS (ESI), m/z calcd for C10H10ClFNO3 (MH-) 244.0182, found 244.0183.

The chemical industry reduces the impact on the environment during synthesis 4-Chloro-3-fluoroaniline. I believe this compound will play a more active role in future production and life.

Reference:
Article; Narumi, Tetsuo; Arai, Hiroshi; Yoshimura, Kazuhisa; Harada, Shigeyoshi; Hirota, Yuki; Ohashi, Nami; Hashimoto, Chie; Nomura, Wataru; Matsushita, Shuzo; Tamamura, Hirokazu; Bioorganic and Medicinal Chemistry; vol. 21; 9; (2013); p. 2518 – 2526;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 367-22-6, name is 4-Chloro-3-fluoroaniline, belongs to chlorides-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 367-22-6, Formula: C6H5ClFN

To a solution containing para- chloro-meta-fluoroaniline (10.0 g, 70.1 mmol) in 600 mL THF at 0 C was added Et3N (9.1 1 mL, 70.1 mmol) followed by ethyl oxalylchloride (7.70 mL, 70.1 mmol) dropwise over 15 minutes. The reaction mixture was warmed to room temperature and stirred for 18 hrs. The reaction mixture was filtered and the filter cake was washed with one-300 mL portion of ethyl acetate. The organic phase was washed with two- 100 mL portions of IM HCl, dried over MgSO4, filtered, and concentrated to give the product. Recrystallization from hot Et2theta gave the product as a colorless crystalline solid: yield 14.4 g (84%); 1H NMR (500 MHz, CDCl3): delta 1.43 (t, J = 7.0 Hz, 3H), 4.42 (q, J= 7.0 Hz, 2H), 7.25 (dq, J= 8.5, 1.0 Hz, 1H), 7.37 (t, J= 8.5 Hz, 1H), 7.72 (dd, J= 10.5, 2.5 Hz, 1H), 8.94 (br, 1H).

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; DANA FARBER CANCER INSTITUTE; JOHNS HOPKINS UNIVERSITY; UNIVERSITY OF PENNSYLVANIA; SODROSKI, Joseph; MADANI, Navid; SCHON, Arne; LA LONDE, Judith, M.; COURTER, Joel, R.; SOETA, Takahiro; NG, Danny; FREIRE, Ernesto; SMITH, Amos, B.; WO2010/53583; (2010); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 367-22-6,Some common heterocyclic compound, 367-22-6, name is 4-Chloro-3-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.

[0075] 4-Chloro-3-fluoroaniline (2g, 13.7 mmol) was dissolved in 60 mL of dichloromethane.Under ice bath, saturated sodium bicarbonate solution (60 mL) was added. The mixture wasstirred at 0 C and triphosgene (1.36g, 4.58 mmol) was added. The mixture was stirred at 0 C for1 h and then extracted with dichloromethane and water. The organic layer was dried with sodiumsulfate and filtered. The filtrate solution was concentrated and the residue was treated with 50mL ofhexanes. The hexane solution was concentrated to remove all solvents. The residue wastaken up in 12 mL ofhexanes and filtered. The solution was concentrated and dried to give 1-chloro-2-fluoro-4-isocyanatobenzene as an offwhite solid (1.69 g). 1H NMR (400 MHz,CHLOROFORM-d) 8 ppm 6.82- 6.90 (m, 1 H) 6.93 (dd, J=9.22, 2.65 Hz, 1 H) 7.31 – 7.41 (m, 1H)

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-3-fluoroaniline, its application will become more common.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; BROTHERTON-PLEISS, Christine, E.; CHEN, Zhi; ERICKSON, Shawn, David; KIM, Kyungjin; LI, Hongju; QIAN, Yimin; SO, Sung-Sau; WOVKULICH, Peter, Michael; YI, Lin; WO2014/56958; (2014); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 367-22-6,Some common heterocyclic compound, 367-22-6, name is 4-Chloro-3-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 suspension of 4-chloro-3-fluoroaniline (10.67 g, 73.3 mmol) and Na2CO3 (24.5 g, 125 mmol) in Et20 (300 ml) at -10 C under N2 was added TFAA (12.23 ml, 88 mmol) dropwise. The mixture was allowed to warm to rt for 18 h. The reaction mixturewas diluted with hexane (300 ml), and filtered. The filtrate was washed with ice-water,10% aq NaHCO3, and brine, dried over Na2SO4, and concentrated. A pale yellow solid obtained as N-(4-chloro-3-fluorophenyl)-2,2,2-trifluoroacetamide (17 g, 96 % yield). MS (ESI) m/z: 242.1 (M+H)t

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-3-fluoroaniline, its application will become more common.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; SMITH II, Leon M.; PINTO, Donald J. P.; CORTE, James R.; EWING, William R.; (163 pag.)WO2016/205482; (2016); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Electric Literature of 367-22-6,Some common heterocyclic compound, 367-22-6, name is 4-Chloro-3-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.

Step C(2S)(M)-[7-[(4-c loro-3-fluorop enyl)amino]-4-(8-fluoro-5-m2-methyl-1 -oxo-1 ,2-dihyd -3-isoquinolinyl][( 1, 1-dimethylethyl)oxy]ethanoic acid[00186] A degassed mixture of (S)(M)-me y 2-(7-bromo-4-(8-fluoro-5-methylchroman-6- yl)-2-methyl-1-oxo-1 ,2-dihydroisoquinolin-3-yl)-2-(tert-butoxy)acetate (22.00 mg, 0.040 mmol), 4-chloro-3-fluoroaniline (1 1.72 mg, 0.081 mmol) and sodium tert-butoxide (1 1 .61 mg, 0.121 mmol) in 1 ,4-Dioxane (1.0 mL) was treated with Pd2(dba)3 (2.084 mg, 2.013 muetaetaomicronIota) and 2- dicyclohexylphosphino-2′-(N,N-dimethyl-amino)biphenyl (3.17 mg, 8.05 mumol) and then irradiated in the microwave at 100 C for 10 minutes. The mixture was diluted with ethyl acetate and washed with saturated sodium bicarbonate, followed by brine. The organic phase was dried over sodium sulfate, filtered and concentrated. The crude residue in methanol (1 .0 mL), tetrahydrofuran (THF) (1 .0 mL) and water (0.2 mL) was treated with lithium hydroxide (19.28 mg, 0.805 mmol) and then heated at 65 C for 4 hours. The mixture was concentrated, water was added and the mixture was adjusted to pH 3 with 1 N hydrochloric acid. The mixture was extracted with ethyl acetate and the extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by reverse phase chromatography to afford the title compound as a tan solid (1 1.8 mg, 49%). 1H NMR (400MHz ,CHLOROFORM-d) delta = 8.10 (m, 1 H), 7.32 – 7.17 (m, 2 H), 6.93 (m, 1 H), 6.89 – 6.74 (m, 3 H), 5.18 (s, 1 H), 4.31 (m, 2 H), 3.71 (s, 3 H), 2.78 – 2.67 (m, 2 H), 2.15 (m, 2 H), 1 .96 (s, 3 H), 1.23 (s, 9 H); LC/MS (m/z) ES+ = 598 (M+1 ).

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-3-fluoroaniline, its application will become more common.

Reference:
Patent; GLAXOSMITHKLINE LLC; DE LA ROSA, Martha Alicia; HAYDAR, Simon, N.; JOHNS, Brian Alvin; VELTHUISEN, Emile Johann; WO2012/102985; (2012); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 367-22-6,Some common heterocyclic compound, 367-22-6, name is 4-Chloro-3-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.

General procedure: A solution of the corresponding 1H-indazole-5-carbaldehyde(2), 1-methyl-1H-indazole-5-carbaldehyde (9) or 1-(2-methoxyethyl)-1H-indazole-5-carbaldehyde (10) (1.0 equiv.),different substituted anilines 3e6 (1.1 equiv.) and acetic acid(0.1 mL/mmol, pH 4e5) in ethanol (3.0 mL/mmol) was stirred underreflux until a precipitation took place. After cooling to roomtemperature, the reaction mixture was sonificated until completeprecipitation. The precipitate formed was filtered and dried at70 C. The crude product was purified by column chromatographyon silica gel (mobile phase: dichloromethane/MeOH 9/1 v/v) andrecrystallized three times from petroleum ether/dichloromethane.

The synthetic route of 367-22-6 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Tzvetkov, Nikolay T.; Stammler, Hans-Georg; Georgieva, Maya G.; Russo, Daniela; Faraone, Immacolata; Balacheva, Aneliya A.; Hristova, Silvia; Atanasov, Atanas G.; Milella, Luigi; Antonov, Liudmil; Gastreich, Marcus; European Journal of Medicinal Chemistry; vol. 179; (2019); p. 404 – 422;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Electric Literature of 367-22-6, A common heterocyclic compound, 367-22-6, name is 4-Chloro-3-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.

Iodine chloride (20.6 ml, 1M solution in DCM, 20.6 mmol) was added dropwise to a solution of 4-chloro-3-fluoroaniline (2 g, 13.7 mmol) in methanol (35 ml) at 0C and the reaction mixture was stirred for 1 h at room temperature. Volatiles were removed under reduced pressure, water was added and the mixture was extracted with dichloromethane. The combined organic layers were washed with water, dried with Na2S04 and evaporated. The remaining residue was purified by chromatography with three consecutive columns (silica gel, heptane/EtOAc 98:2 – 93:7 and twice heptane/EtOAc 98:2 – 95:5) to obtain the title compound (2.51 g, 67%) as dark red solid. MS (ESI): 272.1 (M+H)+.

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; F. HOFFMANN-LA ROCHE AG; CECCARELLI, Simona M.; CONTE, Aurelia; KUEHNE, Holger; KUHN, Bernd; NEIDHART, Werner; OBST SANDER, Ulrike; RUDOLPH, Markus; WO2013/64465; (2013); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Electric Literature of 367-22-6,Some common heterocyclic compound, 367-22-6, name is 4-Chloro-3-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.

General procedure: To the solution of acid in 55 DMF (7ml), were added 56 EDC.HCl (1mmol) and 57 HOBt (1mmol) respectively at 0C. The solution was stirred for 30min followed by addition of 58 (S)-1-phenylethan-1-amine (0.8mmol) and 59 NEt3 (1.33mmol). The reaction mixture was stirred for 1h at 0C and then for 12hat room temperature. The reaction mixture was quenched by saturated NaHCO3 and then extracted with EtOAc. The organic layer was dried with Na2SO4 and concentrated under reduced pressure. The crude residue was purified by column chromatography to obtain pure 60 15a.

The synthetic route of 367-22-6 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Karale, Uttam B.; Krishna, Vagolu Siva; Krishna, E. Vamshi; Choudhari, Amit S.; Shukla, Manjulika; Gaikwad, Vikas R.; Mahizhaveni; Chopra, Sidharth; Misra, Sunil; Sarkar, Dhiman; Sriram, Dharmarajan; Dusthackeer, V.N. Azger; Rode, Haridas B.; European Journal of Medicinal Chemistry; vol. 178; (2019); p. 315 – 328;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 367-22-6, name is 4-Chloro-3-fluoroaniline, belongs to chlorides-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 367-22-6, SDS of cas: 367-22-6

(145d) 4-Amino-Lambda/-(4-chloro-3-fluoro-phenyl)-2-methyl-5-nitro-benzamide 4-Amino-2-methyl-5-nitro-benzoylchloride (950 mg, 4.4 mmol) was added to a stirred mixture of 4-chloro-3-fluoro-aniline (644 mg, 4.4 mmol) and TEA (0.74 ml_, 5.3 mmol) in 80 ml. THF. After stirring for 2h the mixture was concentrated /.vac. The residue was taken up in water and filtrated.Yield: 1.4O g (98%) mass spectrum: (M+H)+ = 324/326 (chlorine isotopes)

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-Chloro-3-fluoroaniline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; PFAU, Roland; ARNDT, Kirsten; DOODS, Henri; HAUEL, Norbert; KLINDER, Klaus; KUELZER, Raimund; MACK, Juergen; PRIEPKE, Henning; STENKAMP, Dirk; WO2010/34796; (2010); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 367-22-6, These common heterocyclic compound, 367-22-6, name is 4-Chloro-3-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.

General procedure: A mixture of substituted anilines (4.70 mmol) in toluene (25 mL) was added to the above reaction solution, followed by stirring for 3 h. Upon completion of the reaction, the resulting mixture was cooled to 20 C.The solid thus obtained was filtered under a reduced pressure and washed with toluene (20 mL). Isopropanol (18 mL) was added to thesolid, which was then stirred for 5 h. The resulting solid was filtered and washed with isopropanol (10 mL). The solid was dried at 50 C in the oven to afford 3a-f as white powder.

Statistics shows that 4-Chloro-3-fluoroaniline is playing an increasingly important role. we look forward to future research findings about 367-22-6.

Reference:
Article; Cai, Zhi-Qiang; Jin, Zheng-Sheng; Zheng, De-Qiang; Hou, Ling; Huang, Guan-Wang; Tian, Jun-Qiang; Wang, Guo-Jiang; Journal of Chemical Research; vol. 40; 9; (2016); p. 573 – 575;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics