Category: 501-29-1

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. 501-29-1, name is 1-Chloro-2-fluoro-4-methoxybenzene, This compound has unique chemical properties. The synthetic route is as follows., Application In Synthesis of 1-Chloro-2-fluoro-4-methoxybenzene

To 1- chloro-2-fluoro-4-methoxybenzene (5.00 g, 31.2 mmol) in cone. H2SO4 (30 mL) at -10 C to 0 C, potassium nitrate (3.47 g, 34.4 mmol) was added portionwise to the reaction mixture. The reaction was stirred at 0 C for 2 h. The reaction was quenched with iced water and filtered. The obtained solids were recrystallized with hexanes to give Intermediate 15A (4.8 g, 75%).

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 501-29-1.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; THIBEAULT, Carl; CLARK, Charles, G.; DELUCCA, Indawati; HU, Carol, Hui; JEON, Yoon; LAM, Patrick, Y., S.; QIAO, Jennifer, X.; YANG, Wu; WANG, Yufeng; WANG, Tammy, C.; WO2014/22349; (2014); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 501-29-1, These common heterocyclic compound, 501-29-1, name is 1-Chloro-2-fluoro-4-methoxybenzene, 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.

Tetrahydrofuran (8.35 L) into a 3-L four-neck flask equipped with a mechanical stirrer, an addition funnel and a temperature probe under N2 atmosphere. Charged 4-Chloro-3-fluoroanisole (1000 g) to a 3-L four-neck flask equipped with a mechanical stirrer, an addition funnel and a temperature probe. Cooled the reaction mass to -60 C. to -70 C. Added n-Butyl Lithium in hexanes (30%, 1.42 kg) in to reaction mass through canula under nitrogen atmosphere slowly, while maintaining the temperature of the reaction mass below -60 C. Maintained the reaction at below -60 C. for 2 h. Meanwhile Iodine solution prepared by dissolving Iodine (2.405 kg) in Tetrahydrofuran (2.4 L) at 25-28 C. Transferred the Iodine solution in step 6 into a clean addition funnel with THF (500 mL) rinse. Added Iodine solution from the addition funnel to the reaction over 120 min while maintaining the internal temperature at <-60 C. Removed cooling bath and allowed to attain -5 C. to 0 C. Submitted the IPC sample when it reaches -5 C. to 0 C.1. A sample was removed at -2 h and checked by HPLC-97.06 AP; Int-01-0.59 AP. Work Up: Quenched the reaction with 20% Na2SO2O3 solution (1.015 kg of sodium thiosulphate dissolved in 5.1 L of DM water) while maintaining the internal temperature at <10 C. Allowed RM to warm to RT. Transfer resulting biphasic mixture into separating funnel, rinse the flask with THF (1.2 L; 1.0-1.5 Vol wrt Int-1), and transfer to separating flask. Removed and retain bottom aqueous phase for further extraction. Concentrated the organic layer. Dissolved concentrated mass in EtOAc (8.0 L; 8.0-8.5 Vol wrt Int-1) Extract the retained aqueous phase with EtOAc (7.1 L: 7.0-7.5 Vol wrt Int-1). Combined all organic phases, Rinse the flask with EtOAc (1.0 L; 1.0-1.5 Vol wrt Int-1). Washed organic phases with DM water (5.7 L; 5.0-6.0 Vol wrt Int-1). Concentrated the organic layer2 on rotovap at 45-50 C. completely. Purification: Added Acetonitrile (5.1 L; 5.0-5.5 vol wrt Int-01). Warmed to 55 C. to dissolve all solid. Rotate the above mass in rotavapor flask at 55 C. for 10 min. Cooled to ambient temperature. Transferred the mass into a clean reactor, rinse the flask with Acetonitrile (1.0 L; 1.0-1.2 vol wrt Int 01) and add rinse into reactor. Added water (1 L; 1.0-1.2 vol wrt Int-01) in to reactor with stirring. Stirred the resulting slurry for 15 min. Added water (5.3 L; 5.0-5.5 Vol wrt Int-01) over 15 min. Stirred the above mass at ambient temperature for 15 min. Unload the mass into a container, rinsed the reactor with water (1 L; 1.0-1.2 vol wrt Int-01), and collected the rinse in same container. Filtered the solid. Rinsed the container with water (1 L; 1.0-1.2 vol wrt Int-01), filtered the rinse. Washed filter cake with water (3.3 L; 3.0-3.5 Vol wrt Int-01). Suck dried for 2 h, then dried at 55 C. in VTD for 15 h. Unload the material. (LOD should be less than 1%). Wt: 1533 g (85.9% yield). Description (color and appearance): Off White crystalline solid. HPLC RT Time 4.897 min Under following conditions: Detector: 210 nm; Injection volume 5.00 muL; Run Time 15 min; Column. YMC UltraHT Pro C18 (50 mm×3.0 mm), 2.0mu; Mobile Phase A-0.05% TFA in MillQ Water; Mobile Phase B-0.05% TFA in Acetonitrile; Flow: 1.0 mL/min; Column Oven-40 C.; Time (min)-0 05 10 12 15; B Conc.-10 90 90 10 10. NMR: (1H NMR, 400 MHz, dmso-d6) delta 7.58 (t, 8.8 Hz, 1H), 6.89 (m, 1H), 3.87 (s, 3H). The synthetic route of 501-29-1 has been constantly updated, and we look forward to future research findings. Reference:
Patent; Bristol-Myers Squibb Company; Yeung, Kap-Sun; Kadow, John F.; US2013/203775; (2013); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Related Products of 501-29-1, A common heterocyclic compound, 501-29-1, name is 1-Chloro-2-fluoro-4-methoxybenzene, molecular formula is C7H6ClFO, 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.

Reference Example 16; 2-Bromo-4-chloro-5-fluoroaisole (Reference Compound No.16-1) A mixture of 4-chloro-3-fluoroanisole (124 muL, 1.00 mmol) and N-bromosuccinimide was dissolved in mixed solvent of anhydrous N,N-dimethylformamide (0.5 mL) and anhydrous dichloromethane (1 mL), and stirred at 40C for 3 days. After cooling down, chloroform (30 mL) and water (30 mL) were added and partitioned. The water layer was extracted with chloroform (30 mL, 2 times). The combined organic layer was washed with saturated brine (30 mL), dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give the titled reference compound (195 mg) as a colorless solid. (Yield 82%)

The synthetic route of 501-29-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Santen Pharmaceutical Co., Ltd; EP1995242; (2008); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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. 501-29-1, name is 1-Chloro-2-fluoro-4-methoxybenzene, This compound has unique chemical properties. The synthetic route is as follows., Formula: C7H6ClFO

To 1- chloro-2-fluoro-4-methoxybenzene (5.00 g, 31.2 mmol) in cone. H2SO4 (30 mL) at -10 C to 0 C, potassium nitrate (3.47 g, 34.4 mmol) was added portionwise to the reaction mixture. The reaction was stirred at 0 C for 2 h. The reaction was quenched with iced water and filtered. The obtained solids were recrystallized with hexanes to give Intermediate 15A (4.8 g, 75%).

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 501-29-1.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; THIBEAULT, Carl; CLARK, Charles, G.; DELUCCA, Indawati; HU, Carol, Hui; JEON, Yoon; LAM, Patrick, Y., S.; QIAO, Jennifer, X.; YANG, Wu; WANG, Yufeng; WANG, Tammy, C.; WO2014/22349; (2014); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Electric Literature of 501-29-1, 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 501-29-1 as follows.

A mixture of 4-chloro-3-fluoroanisole (2.52 g, 15.7 mmol, 1.0 eq.), silver trifluoroacetate (8.57 g, 38.8 mmol, 2.5 eq.), iodine (7.95 g, 31.3 mmol, 2.0 eq.) and chloroform (100 mL) is stirred at r.t. for 16h. The reaction mixture is filtered through a silica plug on a fritted funnel and rinsed with chloroform. The filtrate is washed successively with an aqueous solution of Na2S2O3, water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue is purified by flash chromatography on silica gel to afford the expected product

According to the analysis of related databases, 501-29-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; GALAPAGOS NV; LES LABORATOIRES SERVIER; LABEGUERE, Frederic, Gilbert; HENG, Rama; DE CEUNINCK, Frederic, Andre; ALVEY, Luke, Jonathan; AMANTINI, David; BREBION, Franck, Laurent; DEPREZ, Pierre, Marc, Marie, Joseph; GOSMINI, Romain, Luc, Marie; JARY, Helene; PEIXOTO, Christophe; POP-BOTEZ, Iuliana, Ecaterina; VARIN, Marie, Laurence, Claire; (180 pag.)WO2017/211666; (2017); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 501-29-1, The chemical industry reduces the impact on the environment during synthesis 501-29-1, name is 1-Chloro-2-fluoro-4-methoxybenzene, I believe this compound will play a more active role in future production and life.

4-chloro-3-fluoroanisole (YY-1) in anhydrous THF at -78C under N2(250 mg, 1.56 mmol) was added dropwise a solution of LDA (0.86 mL, 2M,1.71 mmol) and stir for 30 minutes at -78C under N2.DMF (125 mg) was added to the above solution at -78 C under N2.1.71 mmol) and the resulting mixture was stirred at -78 C for 20 minutes.The reaction was quenched with saturated NH4Cl at -78 C. The resulting mixture was heated to 25 C. The mixture was partitioned between EtOAc and H2O.The organic layer was separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated to provide the crude product.The crude product is via a flash column (EtOAc: petroleum ether = 1% to 12%)Purified to provide YY-2 (178 mg, 61%) as a white 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, 1-Chloro-2-fluoro-4-methoxybenzene, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; PFIZER INC.; KUMPF, ROBERT ARNOLD; MCALPINE, INDRAWAN JAMES; MCTIGUE, MICHELE ANN; PATMAN, RYAN; RUI, EUGENE YUANJIN; TATLOCK, JOHN HOWARD; TRAN-DUBE, MICHELLE BICH; WYTHES, MARTIN JAMES; (445 pag.)TW2018/2074; (2018); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 501-29-1,Some common heterocyclic compound, 501-29-1, name is 1-Chloro-2-fluoro-4-methoxybenzene, molecular formula is C7H6ClFO, 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 mixture of 1-chloro-2-fluoro-4-methoxybenzene (5.00 g, 31.1 mmol) in cone. H2S04 (30 mL) at 0-10eC was added portionwise potassium nitrate (3.78 g, 37.4 mmol) and the reaction was stirred at OeC for 2 h. The reaction was quenched with ice water and filtered. The obtained solids were recrystallized with hexanes to give 4.50 g 3 (70%) of 1-chloro-2-fluoro-4-methoxy-5-nitrobenzene. 1HNMR (400 MHz, DMSO- d6) U8.30 (d, J = 2.0 Hz, 1H), 7.61 (d, J = 2.3 Hz, 1H), 3.96 (s, 3H); ESI-MS (m/z) 205.76 (MH)+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Chloro-2-fluoro-4-methoxybenzene, its application will become more common.

Reference:
Patent; LUPIN LIMITED; KUKREJA, Gagan; IRLAPATI, Nageswara, Rao; JAGDALE, Arun, Rangnath; DESHMUKH, Gokul, Keruji; VYAVAHARE, Vinod, Popatrao; KULKARNI, Kiran, Chandrashekhar; SINHA, Neelima; PALLE, Venkata, P.; KAMBOJ, Rajender, Kumar; (366 pag.)WO2018/20474; (2018); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics