Category: chlorides-buliding-blocks

Reference of 1996-29-8, 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. 1996-29-8, name is 1-Bromo-4-chloro-2-fluorobenzene belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

N. 2-CHLORO-5-CYCLOPROPYL-6-FLUOROANILINE The preparation is an adaptation of a method described in Tetrahedron Lett, Vol. 37, p. 6551 (1996). A solution of lithium DIIOSOPROPYL amide is generated by adding n-BuLi (360 mL of 2 M solution in THF) to diisopropylamine (73 g, 0.722 mol) in 500 mL of anhydrous THF while a reaction temperature OF-60C is maintained by cooling in dry-ice acetone bath. After stirring for 30 minutes, 1-bromo-4-chloro-2-fluorobenzene (75 g, 0.36 mol) is added and stirring maintained AT-70C for 2 hours. The cold solution is then transferred, via a canula, under an inert atmosphere to a suspension of solid C02 (100 g, excess) in anhydrous ET2O. The mixture is allowed to warm to room temperature with stirring and then the solvent removed by rotary evaporator. The residual solid is treated with 1 N HCI solution until PH = 3.0 and the mixture is filtered. The white solid that is obtained is suspended in 1000 mL of 2 N HCI solution and stirred for an additional 1 hour. The suspension is filtered to collect a white solid which is air dried, suspended in 100 mL of hexanes and collected to give 2-CHLORO-5-BROMO-6-FLUOROBENZOIC acid. 2-Chloro-5-bromo-6-fluorobenzoic acid (91 g, 0.36 mol) is suspended in CH2CI2 (200 mL) and treated with oxalyl chloride (51 g, 0.40 mol) by dropwise addition, immediately followed by the addition of several drops (0.1 mL) of DMF. The mixture is stirred at room temperature for 3 hours during which time the solid completely dissolves and a clear solution is obtained. The solvent is removed by rotary evaporator and the residue is added to 1000 mL of ammonium hydroxide while stirring at 0C. The product is collected by filtration and washed with water to give 2-chloro-5-bromo-6-fluorobenzamide as a white solid. A solution of sodium methoxide is generated by treating metallic sodium (18 g, 0.78 mol) with 1000 mL of anhydrous methanol by dropwise addition under an inert atmosphere. After the metal is completely consumed the solution is heated at reflux temperature for 30 minutes and then cooled to room temperature. 2-Chloro-5-bromo-6-fluorobenzamide (65 g, 0.26 mol) is added and stirring continued for an additional 30 minutes at room temperature. N-BROMOSUCCINIMIDE (92 g, 0.52 mol) is then slowly added via a powder addition funnel. The reaction mixture is warmed to 60C for 30 minutes during which time foaming is observed. The reaction mixture is cooled to room temperature and most of the solvent is removed by rotary evaporator. The residue is partitioned between EtOAc (1000 mL) and water (1000 mL). The organic layer is separated and washed with water (5 x 500 mL) and then brine (2 x 500 mL). The organic layer is dried (MGS04), filtered and concentrated by rotary evaporator to GIVE N- (2-CHLORO-5-BROMO-6-FLUOROPHENYL)-CARBAMIC acid methyl ester as a light yellow solid (m. p. 107-112C). N-(2-chloro-5-bromo-6-fluorophenyl)-carbamic ester methyl ester (8.65 g, 30.6 MMOL), cyclopropylboronic acid (3.16 g, 36.7 MMOL), potassium phosphate (22.8 g, 107 MMOL), palladium acetate (343 mg, 1.53 MMOL) and tricyclohexylphosphine (858 mg, 3.06 MMOL) are combined and stirred in a two-phase solution comprised of toluene (350 mL) and water (75 mL). The mixture is degassed by repeated alternating application of vacuum and positive nitrogen pressure (10 x). The mixture is heated to 95C for 4 days and then cooled to room temperature. The reaction mixture is partitioned between EtOAc (500 mL) and water (500 mL). The organic phase is washed with water (2 x 250 mL), brine (500 mL) and then dried (MGS04) and concentrated by rotary evaporator. The crude product is purified using flash chromatography (7-14% EtOAc/hexanes). After evaporation of the appropriate fractions the product is further purified by treating a solution in ET20 (100 mL) with charcoal, followed by filtration through Celite and evaporation. N- (2-chloro-5- cyclopropyl-6-fluorophenyl)-carbamic acid methyl ester is obtained as a white crystalline solid (m. p. 100-102C). N-(2-CHLORO-5-CYCLOPROPYL-6-FLUOROPHENYL)-CARBAMIC acid methyl ester (2.3 g, 9.4 MMOL) is dissolved in MeOH (50 mL), water (50 mL) and 30% NAOH solution (50 mL). The reaction mixture is heated to reflux temperature for 3 days and then cooled to room temperature. The reaction is concentrated by rotary evaporator to remove most of the methanol and then partitioned between ET20 (250 mL) and water (250 mL). The aqueous phase is extracted again with ET20 (150 mL) and the-combined organic layers washed with brine (250 mL), dried and concentrated by rotary evaporator. The crude product is purified by bulb-to-bulb distillation. 2-Chloro-5-cyclopropyl-6-fluoroaniline is isolated as a colorless oil (b. p. 120-135C at-20 mm of Hg).

The synthetic route of 1-Bromo-4-chloro-2-fluorobenzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2004/48314; (2004); A1;,
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 210532-25-5 as follows. name: 3,5-Difluorobenzene-1-sulfonyl chloride

A solution of 3-(2-chloro-10H-phenothiazin-10-yl)propan-1-amine hydrochloride (0.080 g, 0.244 mmol) in DMF (1.5 ml) was cooled to 0 C, treated with triethylamine (71.0 muL, 0.513 mmol), and 3,5-difluorobenzenesulfonyl chloride (0.057 g, 0.268 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was poured over saturated aqueous NaCl (50 mL), and extracted with ethyl acetate (3 50 mL). The combined organic extracts were washed with saturated aqueous NaCl (2 50 mL), dried (Na2SO4), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2Cl2 and purified by flash chromatography (SiO2, 0-35% ethyl acetate-hexanes) to afford the title compound as a white solid triturated from ethyl ether-hexanes (0.0736 g, 65%). 1H NMR (600 MHz, CDCl3) 7.17-7.22 (4H, m), 7.11 (1H, d, J = 8.2 Hz), 7.01 (1H, t, J = 7.6 Hz), 6.95 (2H, m), 6.85 (1H, d, J = 8.1 Hz), 6.81 (1H, s), 5.23 (1H, t, J = 5.9 Hz), 3.93 (2H, t, J = 5.8 Hz), 3.13 (2H, dd, J = 12.2, 6.1 Hz), 1.97 (2H, quintet, J = 5.9 Hz); 13C NMR (150 MHz, CDCl3) 163.7 (d, J = 48.0 Hz), 162.0 (d, J = 44.2 Hz), 146.5, 144.5, 143.4 (t, J = 34.3 Hz), 133.8, 128.6, 128.2, 127.9, 126.0, 124.8, 123.9, 123.3, 116.3 (d, J = 52.7 Hz), 110.6 (dd, J = 85.3, 26.0 Hz), 108.3 (t, J = 100.6 Hz), 45.3, 42.0, 26.3; LCMS m/z 467.1 ([M + H+], C21H17ClF2N2O2S2 requires 467.0).

According to the analysis of related databases, 210532-25-5, the application of this compound in the production field has become more and more popular.

Reference:
Article; Kastrinsky, David B.; Sangodkar, Jaya; Zaware, Nilesh; Izadmehr, Sudeh; Dhawan, Neil S.; Narla, Goutham; Ohlmeyer, Michael; Bioorganic and Medicinal Chemistry; vol. 23; 19; (2015); p. 6528 – 6534;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 4863-91-6,Some common heterocyclic compound, 4863-91-6, name is 3-Chloro-5-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) 4-Bromo-3-chloro-5-fluoroaniline 3-Chloro-5-fluoroaniline (2061 mmol, 300 g) was dissolved in ACN (3000 ml) and the solution cooled to 0 C. NBS (2061 mmol, 367 g) was added to the reaction mixture in small portions keeping the temperature below 10 C. Reaction mixture was stirred at 10+-5 C. for 3.5 h. 10% Aqueous NaHSO3 was added and the reaction mixture was concentrated under vacuum to remove organic solvents. Water and DCM was added, stirred for 15 min and the phases were separated. The water phase was extracted with DCM. The combined organics were washed with water. The organic phase was evaporated. 2-Propanol was added to the residue and distilled until the steam temperature was 80 C. Water was added and the temperature was kept at 40+-10 C. The mixture was cooled to 5 C. and stirred for 4 h. The precipitate was removed by filtration, washed with water and dried under vacuum. 440.7 g of the title compound was obtained. 1H-NMR (400 MHz, DMSO-d6): delta 5.87 (s, 2H), 6.42-6.49 (m, 1H), 6.62-6.66 (m, 1H).

The synthetic route of 4863-91-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ORION CORPORATION; Toermakaengas, Olli; Wohlfahrt, Gerd; Salo, Harri; Ramasurbamanian, Rathna Durga; Patra, Pranab Kumar; Martin, Arputharaj Ebenezer; Heikkinen, Terhi; Vesalainen, Anniina; Moilanen, Anu; Karjalainen, Arja; US2014/94474; (2014); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 26487-67-2, 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. 26487-67-2 name is 1-(2-Chloroethyl)azepane hydrochloride, 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 11-Cyano-11-[2(hexamethyleneimino)ethyl]-6,11-dihydrodibenz[b,e]oxepin oxalate To a solution of 11-cyano-6,11-dihydrodibenz[b,e]oxepin of Example 1A (7.2 g; 0.032 mole) in dry DMF (110 ml) at 5° C. is added sodium hydride (1.9 g; 0.08 mole) portionwise under a nitrogen atmosphere. After stirring at ambient temperature for 11/2 hours, the reaction is cooled to 10° C. and 2-(hexamethylene-imino)ethyl chloride hydrochloride (6.9 g; 0.035 mole) is added portionwise. Stirring is continued at 100° C. for 21/2 hours. The reaction is cooled and poured into two liters of ice water, extracted with ether and the ether back extracted with 2 N HCl. The acidic extracts are combined and made basic with sodium hydroxide. After extracting with ether, washing with a saturated NaCl solution and drying (K2 CO3), the ether is removed in vacuo to provide 3.0 g of an oil (27percent).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-(2-Chloroethyl)azepane hydrochloride, and friends who are interested can also refer to it.

Reference:
Patent; Hoechst-Roussel Pharmaceuticals Inc.; US4335122; (1982); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 14862-52-3,Some common heterocyclic compound, 14862-52-3, name is 3,5-Dibromochlorobenzene, molecular formula is C6H3Br2Cl, 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 1 Synthesis of 3,5-diphenylchlorobenzene The compound entitled was synthesized in accordance with the following scheme. Into a 1 L four-necked glass flask equipped with a thermometer, a reflux condenser and a stirrer, 3,5-dibromochlorobenzene 20.0 g (74.0 mmol), phenylboronic acid 27.0 g (222 mmol), 2.0 mol/l sodium carbonate aqueous solution 285 ml (570 mmol), and toluene:tetrahydrofuran (1:1) solution 500 ml were added, and nitrogen was passed through the solution for 2 hours and 30 minutes. Tetrakistriphenylphosphine palladium(0) 4.28 g (3.70 mmol) was then added, which was reacted for 28 hours at 73 to 75 C. with stirring followed by further addition of phenylboronic acid 4.10 g (33.6 mmol) and tetrakistriphenylphosphine palladium(0) 1.10 g (950 mumol) and reaction for 24 hours at 73 to 75 C. with stirring. After completion of the reaction, the reaction mixture was cooled down to room temperature and separated with the addition of water and toluene, and after the water layer was extracted with toluene and after the organic layers were combined and washed with water, it was dried with anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the obtained concentrate was purified by silica-gel column chromatography (eluent: hexane) to obtain 3,5-diphenylchlorobenzene 16.0 g as white solid (isolation yield; 82%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3,5-Dibromochlorobenzene, its application will become more common.

Reference:
Patent; UBE INDUSTRIES, LTD.; US2011/140044; (2011); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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. 445-13-6, name is 3-Chloro-4-(trifluoromethyl)aniline belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. HPLC of Formula: C7H5ClF3N

To a stirred solution of 3-chloro-4-(trifluoromethyl)aniline (AS) (10 g, 51.2 mmol) in glycerol (120 mL) were added sulfamix (17.3 g, 76.8 mmol), FeS04.7H20 (2.9 g, 10.7 mmol) followed by boric acid (5.06 g, 81.9 mmol) at RT. The reaction mixture was cooled to 0 C; Conc.H2S04 (35 mL) was added to the reaction mixture and heated at 145 C for 3 h. After consumption of the starting material (by TLC), the reaction was quenched with cold water and neutralized with NaHC03. The aqueous layer was extracted with CH2CI2 (3 x 500 mL). The combined organic phases were washed with water (100 mL), brine (100 mL), dried over anhydrous Na2S04> filtered and concentrated in vacuo. The obtained crude material was purified by silica gel column chromatography eluting with 30% EtOAc/hexane to afford AT (mixture of 5,6- and 6,7-regio isomers) (4 g, 17.2 mmol, 34%) as syrup.To a stirred solution of AT (mixture of 5,6- and 6,7-regio isomers) (4 g, 17.2 mmol) in EtOAc (20 mL) was added m-CPBA (7.4 g, 43 mmol) at 0 C and the reaction mixture was stirred at RT for 12 h. After consumption of the starting material (by TLC), the reaction mixture was concentrated under reduced pressure. The crude material was purified by silica gel column chromatography eluting with 10% MeOH/CH2Ci2 to afford AU (mixture of 5,6- and 6,7-regio isomers) (2 g, 8.06 mmol, 47.6%) as yellow solid.To a stirred solution of AU (mixture of 5,6- and 6,7-regio isomers) (5.0 g, 20.1 mmol) in ACN (50 mL) was added Et3N (7.1 g, 70.3 mmol) followed by TMSCN (6.9 g, 70.3 mmol) at 0 C under an inert atmosphere. The reaction mixture was stirred at RT for 14 h. The volatiles were evaporated under reduced pressure and the crude material was purified by silica gel column chromatography eluting with 8% EtOAc/Hexane to afford AV (6,7-isomer) (2.0 g, 7.75 mmol, 38.4%) as a brown solid.

The synthetic route of 445-13-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; VIAMET PHARMACEUTICALS, INC.; HOEKSTRA, William, J.; SCHOTZINGER, Robert, J.; RAFFERTY, Stephen, William; WO2012/64943; (2012); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Electric Literature of 102-49-8, 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. 102-49-8, name is 3,4-Dichlorobenzylamine belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

General procedure: In a 50mL round bottom flask, Compound 6 (0.5g, 0.6698mmol), potassium iodide (1.11g, 0.698mmol), and cyclopropylamine (2.43mL, 2.00g, 35mmoL) in isopropanol (5mL) was shocked to dissolve at 50°C. The reaction was insulated. Reaction progress was monitored by TLC. After reaction completion, it was concentrated. The residue was dissolved in water (50mL) and ethyl acetate (100mL). The aqueous layer was washed with ethyl acetate (3 × 50mL). The combined organic phases was washed with saturated aqueous sodium bicarbonate (50mL) and brine (40mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated to give the crude product. Purified by chromatography on silica gel eluting with methanol:dichloromethane:ammonia (4:95.6:0.4 to 6:93.5:0.4) to give 0.38g of the title compound (2R,3S,4R,5S,8R,10R,11R,12S,13S,14R)-13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-4-C-[(cyclopropylamino)methyl]-alpha-L-ribopyranosyl)oxy]-2-ethyl-3,4,10-trihydroxy-3,5,8,10,12,14-hexamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-beta-D-hexylxylopyranosyl]oxy]-1-oxa-7-azacyclopentadecan-15-one For Examples 5 to 80, R is described in Table 1 and R in nitrogen or sulfur are directly connected to R3 methylene. R’ is H for Examples 5 to 80. Example 5 prepared according to General Procedure 1, General Procedure 2, and General Procedure 3 was followed for Examples 6-80 with specific reaction time and basis listed in the table. In the table, structure, yield and mass spectrometry ( “MassSpec”) data are given for the final compound.

The synthetic route of 3,4-Dichlorobenzylamine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Pulike Biological Engineering, Inc.; Liu, Xingjin; Zhang, Xuke; (77 pag.)CN105669798; (2016); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

These common heterocyclic compound, 210532-25-5, name is 3,5-Difluorobenzene-1-sulfonyl chloride, 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. SDS of cas: 210532-25-5

General procedure: To a solution of intermediate 13 (10mmol) and triethylamine (15mmol) in dichloromethane (20ml), a solution of appropriate acyl chlorides or sulfonyl chlorides (1.05 eq) in dichloromethane (3ml) was added dropwise at room temperature overnight. The mixture was washed with saturated aqueous sodium bicarbonate and brine. After removing the solvent under reduced pressure, the crude product was purified by flash chromatography on silica gel to yield the intermediates 14a-n, 15a-k, 16a-h, 17a-m. Subsequently, to a solution of the above intermediates (2mmol) in methanol/H2O (75%, 10ml) was added lithium hydrate (2.4mmol). The resulting mixture was allowed to warm up to 60C for 4h. The reaction mixture was allowed to cool to room temperature and concentrated under pressure to remove methanol. The resulting mixture was diluted by water and acidified with aqueous HCl (1mol/L) till pH=3. The white solid was collected by filtration, washed with water three times and dried to give the target compounds.

The synthetic route of 3,5-Difluorobenzene-1-sulfonyl chloride has been constantly updated, and we look forward to future research findings.

Reference:
Article; Guo, Yongzhi; Zhao, Yuqian; Wang, Guan; Chen, Yi; Jiang, Yingnan; Ouyang, Liang; Liu, Bo; European Journal of Medicinal Chemistry; vol. 143; (2018); p. 402 – 418;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

7051-16-3, name is 1-Chloro-3,5-dimethoxybenzene, belongs to chlorides-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Recommanded Product: 1-Chloro-3,5-dimethoxybenzene

Example 9 Synthesis of Aromatic Amines Copper iodide (0.05 mmol), ligand L-II-71 (0.05 or 0.1 mmol), potassium phosphate (1.1 mmol) were added into a 10 mL of Schlenk tube. The tube was then evacuated and backfilled with argon (this sequence was repeated three times), and then aryl chloride (1.0 mmol), 1 mL of DMSO and ammonium hydroxide (2.0 mmol) were added. The reaction mixture was well stirred at 110C. or 120C. for 24 hours. After cooling, water and ethyl acetate were added and mixture was separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic phase was dried over anhydrous sodium sulfate. After concentration, the residue was purified by column chromatography to give the product aromatic amines.

The synthetic route of 7051-16-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CE Pharm CO., LTD; Ma, Dawei; Zhou, Wei; Fan, Mengyang; Wu, Haibo; Yin, Junli; Xia, Shanghua; (73 pag.)US10500577; (2019); B2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 19752-55-7, A common heterocyclic compound, 19752-55-7, name is 1-Bromo-3,5-dichlorobenzene, molecular formula is C6H3BrCl2, 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.

Compound 7B (31.2 g, 55.57 mmol) and Reagent 4 (12.6 g, 55.57 mmol) were put into 300 ml of tetrahydrofuran under a nitrogen atmosphere, and the resulting mixture was stirred and refluxed. Thereafter, potassium carbonate (23.0 g, 167.70 mmol) was dissolved in 800 ml of water, the resulting solution was introduced into the mixture, the resulting mixture was sufficiently stirred, and then tetrakistriphenyl-phosphinopalladium (1.9 g, 1.67 mmol) was introduced thereinto. After the reaction for 12 hours, the temperature of the product was lowered to normal temperature and a produced solid was filtered. After the filtration, the solid was washed with 100 ml of tetrahydrofuran, 500 ml of ethyl acetate, 500 ml of water, and 300 ml of ethanol. The resulting product was dried to prepare Compound 7C (26 g, 80percent). Reagent 4 was purchased from Aldrich.

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; LG Chem, Ltd.; Jung, Min Woo; Lee, Dong Hoon; Huh, Jungoh; Jang, Boonjae; Kang, Minyoung; Heo, Dong Uk; Han, Miyeon; (52 pag.)US2018/244630; (2018); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics