Month: June 2021

Electric Literature of 399-94-0, These common heterocyclic compound, 399-94-0, name is 1-Bromo-2,5-difluorobenzene, 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.

Method B:To a solution of 1-bromo-2,5-difluorobenzene (42.2 g, 0.218 mol) in toluene (85 mL) at -10 to -5 C. was added iPrMgCl/LiCl solution (1.0 M in THF, 240 mL, 0.24 mol) dropwise over 1.5 h. The reaction solution was then aged for 30 min at -10 to -5 C.In a separate vessel, Weinreb amide 4 (28 g, 0.109 mol) was dissolved in THF (112 mL), cooled to 15 C. and then charged to the above Grignard solution over about 30 min, while the internal temperature was maintained at -10 to -5 C. The reaction mixture was then warmed to 20 C. over 1 h, and aged for additional 1 h at 20 C. for complete reaction. The reaction mixture was quenched with an aqueous HCl solution (32.5 g of concentrated hydrochloric acid in 110 mL of water) at 0 to 10 C. over 30 min. The organic phase was washed with 10% NaCl solution (200 mL×2). The organic phase was solvent switched to iPrOH (final volume about 270 mL) and water (380 mL) was added over 1 h at 20 C. Solids were filtered and washed with 40% iPrOH in water (60 mL×2). The wet cake was dried under vacuum at 45 C.1H-NMR (500 MHz, CDCl3): delta 7.56 (m, 1H), 7.25 (m, 1H); 7.15 (m, 1H), 5.67 (d, J=7.3 Hz, 1H), 5.24 (m, 1H), 2.91 (m, 1H), 2.68 (m, 1H), 2.00 (t, J=2.43, 1H), 1.45 (s, 9H). 13C-NMR (125 MHz, CDCl3): delta 159.03 (dd, J=245.5, 1.8 Hz), 157.4 (d, J=248.0 Hz), 124.6 (dd, J=15.4, 6.2 Hz), 122.2 (dd, J=24.6, 9.8 Hz), 118.4 (dd, J=27.1, 8.0 Hz), 117.6 (DD, J=25.2, 3.7 Hz), 80.4, 78.4, 72.1, 57.9 (d, J=7.5 Hz), 28.5, 22.3.

The synthetic route of 399-94-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Xu, Feng; Kim, Mary M.; Kohmura, Yoshinori; Sladicka, Tricia; Rosen, Jonathan D.; Zacuto, Michael J.; US2009/187028; (2009); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Related Products of 656-64-4,Some common heterocyclic compound, 656-64-4, name is 3-Bromo-4-fluoroaniline, molecular formula is C6H5BrFN, 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.

Water (11.38 mL) was added to a solution consisting of 3-bromo-4-fluoroaniline (10 g, 53 mmol), sodium 3-nitrobenzenesulfonate (21 g, 95 mmol), and propane-1,2,3-triol (14 g, 0.15 mol). The resultant mixture was carefully treated with concentrated H2SO4 (21.1 mL), and then heated to 150 C. with stirring for 2 h before cooling to room temperature. The resultant mixture was carefully neutralized with 5 N sodium hydroxide, filtered through a pad of diatomaceous earth, and the pad was washed with dichloromethane (50 mL). The resultant mixture was extracted with dichloromethane (100 mL*3) and the combined organic extracts were dried over Na2SO4, filtered, and the filtrate concentrated to give a crude product, which was purified by FCC (petroleum ether: ethyl acetate=3:1) to afford the compounds 62a and 62a-1 (9.5 g, 80%). LCMS (ESI): RT=0.64, 0.68 min, mass calcd. for C9H5BrFN 224.96, m/z found 227.6 [M+H]+. 1H NMR (400 MHz, CDCl3) delta 8.96-8.87 (m, 2H), 8.55 (d, J=8.8 Hz, 1H), 8.39 (d, J=6.8 Hz, 1H), 8.15-8.07 (m, 2H), 7.60-7.42 (m, 4H). A mixture of 5-bromo-6-fluoroquinoline, 62a and7-bromo-6-fluoroquinoline, 62a-1 (10 g, 22 mmol), (diphenylmethylene)hydrazine (4.3 g, 22 mmol), 2,2?-bis(diphe- nylphosphino)-1,1?-binaphthyl (1.4 g, 2.2 mmol), palladium (II) acetate (0.50 g, 2.2 mmol), t-l3uONa (6.4 g, 66 mmol), and 1,4-dioxane (150 mE) was stirred at 1000 C. for 16 h. The suspension was filtered through a pad of diatomaceous earth and the pad was washed with ethyl acetate (30 mE). The filtrate was concentrated to dryness under reduced pressure to give a crude product, which was added into water (30 mE). The resultant mixture was extracted with ethyl acetate (50 mEx3). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and the filtrate concentrated to dryness under reduced pressure to afford the crude product, which was purified by FCC (petroleum ether:ethyl acetate=3:1) to afford compounds 62b and 62b-1 (5 g, 33%). ECMS (ESI): RT=0.68 mm, mass calcd. for C22H,6FN3 341.13, mlz found 341.9 [M+H]. Concentrated HC1 (10 mE) was added to a solution consisting of 5-(2-(diphenylmethylene)hydrazinyl)-6-fluo- roquinoline, 62b and 7-(2-(diphenylmethylene)hydrazinyl)- 6-fluoroquinoline, 62b-1 (5.0 g, 7.3 mmol) and EtOH (3 mE). The resultant solution was stirred at room temperature for 16 h. The resultant mixture was treated with water (30 mE) and extracted with dichloromethane (30 mEx3). Theaqueous phase was basified with 5 M NaOH to pH 12. Thesuspension was filtered and the collected solids were washedwith water (20 mE) and dried under reduced pressure toafford compounds 62c and 62c-1 (1.2 g, 46%). ECMS (ESI):RT=1.24 mm, mass calcd. for C9H8FN3 177.07, mlz found178.1 [M+H].

The synthetic route of 656-64-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Janssen Biotech, Inc.; Lu, Tianbao; Allison, Brett Douglas; Barbay, Joseph Kent; Connolly, Peter J.; Cummings, Maxwell David; Diels, Gaston; Edwards, James Patrick; Kreutter, Kevin D.; Philippar, Ulrike; Shen, Fang; Thuring, Johannes Wilhelmus John Fitzgerald; Wu, Tongfei; (412 pag.)US2018/170909; (2018); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Electric Literature of 615-54-3, These common heterocyclic compound, 615-54-3, name is 1,2,4-Tribromobenzene, 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.

[00149] A suspension of compound 1 (27.0 g, 85.7mmol), potassium vinyltrifluoroborate (compound 4) (41.4 g, 0.31 mol), PdCI2 (0.76g, 4.3mmol), Cs2C03 (125.6 g, 0.39 mol) and PPh3 (3.38g, 12.9mmol) in a mixture of THF and water (400ml_, THF/H20 9:1 ) was heated at reflux for 17h under a nitrogen atmosphere. The reaction was cooled to room temperature and the solvent removed by evaporation. The residue obtained was diluted with water (300ml_) and extracted with ethyl acetate (100ml_ x 3). The combined organic extracts were washed with water (200mL) and brine (100ml_), dried (Na2S04) and concentrated to give the crude product, which was purified by column chromatography (neat petroleum ether), illustrated below, to afford compound 5 (1 1.40g, 85%) as an oil.

The synthetic route of 615-54-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BOULOS & COOPER PHARMACEUTICALS PTY LTD; BOULOS, Ramiz; FEUTRILL, John; (105 pag.)WO2017/27933; (2017); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

These common heterocyclic compound, 399-94-0, name is 1-Bromo-2,5-difluorobenzene, 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. Formula: C6H3BrF2

General procedure: To an oven-dried 25 mL Schlenk tube containing a stirring bar was added 4.5 mg Pd(OAc)2 (0.02 mmol), 15.7mg nBuPAd2 (0.44 mmol), 2-bromofluorobenzene (0.50 mmol), salicylaldehyde (0.50 mmol), potassium carbonate (1.0 mmol). The Schlenk tube was vacuumed and then purged with argon before DMF (2.0 mL) was injected using a syringe. Afterwards the Schlenk tube in the ice bath was degassed by evacuation and back fillingwith argon three times. The reaction mixture was then stirred for 12 h at 120 C. After the reaction was complete,the reaction mixture was diluted with water (5 mL), extracted with ethyl acetate (3 x 10 mL) and dried withanhydrous Na2SO4. After filtration and addition of silica gel into the solution, the organic solvent was reduced evaporated. The crude product was purified by column chromatography using ethyl acetate/n-pentane.

The synthetic route of 1-Bromo-2,5-difluorobenzene has been constantly updated, and we look forward to future research findings.

Reference:
Article; Shen, Chaoren; Wu, Xiao-Feng; Synlett; vol. 27; 8; (2016); p. 1269 – 1273;,
Bromide – Wikipedia,
bromide – Wiktionary

Electric Literature of 112734-22-2, 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 112734-22-2 as follows.

General procedure: To a stirred solution of N-(t-butoxycarbonyl)glycine (1 mmol) in CH2Cl2 (10 mL) was added CDI (1.1 mmol), and the resulting mixture was stirred at room temperature for 1 h. To the resulting mixture was added amine (1 mmol), and the reaction mixture was stirred at room temperature for 24 h. The solvent was removed under reduced pressure, and the residue was chromatographed on silica gel (20 g, hexane : acetone = 6 : 1 ~ 3 : 1) to give the corresponding amide.

According to the analysis of related databases, 112734-22-2, the application of this compound in the production field has become more and more popular.

Reference:
Article; Mori, Hisashi; Wada, Ryogo; Li, Jie; Ishimoto, Tetsuya; Mizuguchi, Mineyuki; Obita, Takayuki; Gouda, Hiroaki; Hirono, Shuichi; Toyooka, Naoki; Bioorganic and Medicinal Chemistry Letters; vol. 24; 16; (2014); p. 3732 – 3735;,
Bromide – Wikipedia,
bromide – Wiktionary

Synthetic Route of 4549-33-1, 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. 4549-33-1, name is 1,9-Dibromononane, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of 6-(4-chlorophenyl)-1-methyl-8-(1H-pyrazol-4- yl)spiro[benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine-4,1′-cyclopropane] (59-2) (100 mg, 249 mumol) in DMF(1.5 mL) was added Cs2CO3 (121 mg, 373 mumol) and 1,9-dibromononane (85.2 mg, 298 mumol) . The mixture was stirred for 4h at 30 C. Water(30 mL) and EA(30 mL*2) were added. The Combined organic layers was dried over Na2SO4 and concentrated, purified with prep- TLC (EA=100%) to give 8-(1-(9-bromononyl)-1H-pyrazol-4-yl)-6-(4-chlorophenyl)-1- methylspiro[benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine-4,1′-cyclopropane] (113-1) (39.2 mg, 26.1 %) as an oil. LCMS (ES+): m/z= 605 [M + H]+

The chemical industry reduces the impact on the environment during synthesis 1,9-Dibromononane. I believe this compound will play a more active role in future production and life.

Reference:
Patent; C4 THERAPEUTICS, INC.; PHILLIPS, Andrew, J.; NASVESCHUK, Chris, G.; HENDERSON, James, A.; LIANG, Yanke; FITZGERALD, Mark, E.; MICHAEL, Ryan, E.; (790 pag.)WO2017/197056; (2017); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Synthetic Route of 64248-56-2, A common heterocyclic compound, 64248-56-2, name is 2-Bromo-1,3-difluorobenzene, molecular formula is C6H3BrF2, 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.

Example A-22 4-(2,6-Difluoro-phenyl)-1H-indole To a mixture of 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole (11.34 g, 46.6 mmol), and 1-bromo-2,6-difluorobenzene (9 g, 46.6 mmol) in 1,2-dimethoxyethane (204 mL) were added Palladium catalyst Pd(PPh3)4 (1.62 g, 1.4 mmol) and the freshly prepared sodium carbonate solution (15.19 g in 66 mL of water). The system was degassed and then charged with nitrogen. The degas procedure was repeated for three times. The mixture was stirred under nitrogen at 110 C. oil bath for overnight. TLC showed the completion of the coupling reaction. The mixture was cooled to room temperature, diluted with ethyl acetate, and separated from water layer. The ethyl acetate solution was washed with brine, and dried over Na2SO4. After filtration, the solvents were evaporated, and the crude product was purified by a silica gel column to give 9.77 g (91%) of 4-(2,6-difluoro-phenyl)-1H-indole.

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; Sugen, Inc.; US2003/69297; (2003); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Synthetic Route of 4549-33-1, A common heterocyclic compound, 4549-33-1, name is 1,9-Dibromononane, molecular formula is C9H18Br2, 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.

Synthesis of Compound 9.1 [0189] To a solution of 2075-45-8 (1.30 g, 8.84 mmol, 1.0 eq) in CH3CN (20 ml) were added K2C03 (1.41 g, 13.26 mmol, 1.5 eq) and 4549-33-1 (5.05 g, 7.68 mmol, 2.0 eq). The reaction mixture was stirred at 65 C for 16 h. After cooling down to ambient temperature, the resulting solution was diluted with H20 (100 mL), extracted with ethyl acetate (100 ml). The organic layer was dried over anhydrous sodium sulphate and concentrated in vacuo. The residue was purified by silica gel column (PE / EA = 10 / 1) to give 9.1 (2.08 g, yield: 66%) as a white solid. 1H NMR (400 MHz, CDC13) delta: 7.44 (s, 1H), 7.38 (s, 1H), 4.09 (t, J = 1.2 Hz, 2H), 3.41 (t, J = 1.2 Hz, 2H), 1.87-1.80 (m, 4H), 1.42-1.37 (m, 2H), 1.29-1.24 (m, 8H); ESI-MS (M+H) +: 351.0.

The synthetic route of 4549-33-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BIOGEN IDEC MA INC.; JENKINS, Tracy; VESSELS, Jeffery; WO2014/143672; (2014); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

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. 52997-43-0, name is 7-(Bromomethyl)pentadecane, A new synthetic method of this compound is introduced below., Safety of 7-(Bromomethyl)pentadecane

General procedure: The general procedure for the alkylation of fluorene (C-alkylation) is as follows. A two-neck flask with a three-way stopcock and a rubber septum was charged with fluorene (4mmol, 0.664 g) and dry THF (20 mL). KOtBu (12mmol, 1.346 g) was added to the flask at room temperature, then the mixture was heated at reflux for 20min. The flask was allowed to reach room temperature with stirring for 30min. 1-Bromododecane (8.8mmol, 2.20 g) was slowly added to the reaction mixture at 0 C, then again the flask was allowed to reach room temperature with stirring for overnight. 2.2.1 The First Posttreatment: After checking TLC and the 1HNMR spectrum, the reaction mixture refluxed for one hour. The reaction was quenched by the addition of sat. NH4Cl aqueous solution, extracted into n-hexane (50 3 mL), was hed successively with water, brine, dried (anhydrous Na2SO4) and concentrated by rotary evaporator to afford the reaction mixture(including the target dialkylated fluorene and olefin.). 2.2.2 The Second Posttreatment: 2-(a): To a mixtureof the crude mixture of the first posttreatment, 5wt% Pd/C(0.100 g) and acetic acid (AcOH, 4mmol) in THF (10 mL) were slowly added portionwise NaBH4 (4mmol, 0.151 g), andthe resulting mixture was stirred at room temperature for 12 hours. Thereafter, the mixture was filtered and the precipitate was washed with hexane and concentrated by rotary evaporatorfor NMR measurement. 2-(b): Since the alkylation was an almost quantitative reaction, the expected amount of olefin in the mixture was equalto the excess amount of starting alkyl halide (0.8mmol in the above case). It could be assumed that 0.8 mmol of olefin should be treated with the small excess of 9-BBN (1.2mmol, 1.5 eqvs olefin). A two neck flask with a three-way stopcock and a rubber septum was charged with the above reaction mixture and dry THF (20 mL). 0.5M 9-BBN in THF (1.2mmol, 2.4mL) was added to the flask at 0 C and then the flask was allowed to warm to room temperature and stirred for one hour. To quench the remaining 9-BBN in the reaction, aminoalcohol (2-dimethylaminoethanol, 0.5mmol, 0.045 g) was added to the flask and stirred for another hour. 39 The final reaction mixture was quenched by the addition of water (5 mL), extracted into EtOAc (50 3 mL), washed successively with water, brine, dried (anhydrous Na2SO4) and concentrated by rotary evaporator to afford the crude mixture. 2.2.3 The Third Posttreatment: The crude product was purified on short silica-gel [5 cm (diameter of column) 10 cm (length of deposition of silica-gel) was enough for this scale] with n-hexane as eluent to give the dialkylated fluorene.

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:
Article; Okamoto, Ken; Lu, Fengniu; Nakanishi, Takashi; Bulletin of the Chemical Society of Japan; vol. 91; 8; (2018); p. 1258 – 1263;,
Bromide – Wikipedia,
bromide – Wiktionary

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. 14659-58-6, name is 2-Bromo-5-fluoro-1,3-dimethylbenzene, This compound has unique chemical properties. The synthetic route is as follows., category: bromides-buliding-blocks

A solution of 2-bromo-5-fluoro-1,3-dimethylbenzene (25 g, 123 mmol) in tetrahydrofuran (300 mL) was cooled to -78 C and n-butyllithium (59.1 mL, 148 mmol) wasadded dropwise at a rate to keep the internal temperature at or below -75 C. The mixture was stirred for 2 hours and then trimethylborate (16.51 mL, 148 mmol) was added and the mixture stirred for 3 hours at -78 C, then warmed to ambient temperature. After 4 hours, the mixture was cooled to -10 C and a precooled solution of NaOH (7.39 g, 185 mmol) and 30 % hydrogen peroxide (201 mL, 1970 mmol) was added. Once the addition was completethe mixture was allowed to warm to ambient temperature overnight. The pH of the mixture was adjusted to pH 1 with 2M HC1. 400 mL of ethyl ether and 200 mL of water were added and the layers were separated. The aqueous layer was extracted with 3 x 200 mL of ether, and the combined organic layers were washed with saturated NaHCO3 and saturated Na5203, then stirred with a saturated aqueous Na5205 solution (200 mL) for 15 minutes. The organicphase was dried with anhydrous magnesium sulfate, filtered, and concentrated. The residues were taken up in 1/1 diethyl ether/pentane and flushed through a silica plug. Concentration of the filtrate provided 11 .47g (67%) of the title compound.

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 14659-58-6.

Reference:
Patent; ABBVIE INC.; ABBVIE PHARMACEUTICAL TRADING (SHANGHAI) CO., LTD.; FIDANZE, Steven D.; HASVOLD, Lisa A.; LIU, Dachun; MCDANIEL, Keith F.; PRATT, John; SCHRIMPF, Michael; SHEPPARD, George S.; WANG, Le; LI, Bing; (191 pag.)WO2017/177955; (2017); A1;,
Bromide – Wikipedia,
bromide – Wiktionary