Category: chlorides-buliding-blocks

These common heterocyclic compound, 110407-59-5, name is 2-Chloro-4-fluorobromobenzene, 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. Computed Properties of C6H3BrClF

Step 1 Ethyl 2′-chloro-4′-fluorobiphenyl-2-carboxylate To a reaction vessel were added 1-bromo-2-chloro-4-fluorobenzene (25 g), ethyl 2-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)benzoate (46 g), toluene (125 ml), water (125 ml) and tripotassium phosphate (50.5 g), and the reaction vessel was substituted with argon. To this mixture was added dichlorobis(triphenylphosphine)palladium(II) (1.67 g) and the mixture was stirred at an oil bath temperature 110 C. for 3 hr. The reaction vessel was removed from the oil bath, and water (125 ml) was added to the reaction mixture. The mixture was stirred at room temperature for 1 hr and filtered through celite. The filtrate was partitioned by pouring into a separating funnel. The aqueous layer was extracted with toluene, and combined with the organic layer. The organic layer was washed twice with water (125 ml), dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to give the title compound (41.8 g). The obtained solid was used for the next reaction without further purification. 1H-NMR (400 MHz, CDCl3) delta: 8.06-8.02 (1H, m), 7.60-7.54 (1H, m), 7.52-7.45 (1H, m), 7.27-7.16 (3H, m), 7.06-7.00 (1H, m), 4.18-4.09 (2H, m), 1.11-1.06 (3H, m).

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

Reference:
Patent; JAPAN TOBACCO INC.; Motomura, Takahisa; US2014/296316; (2014); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

These common heterocyclic compound, 623-12-1, name is 1-Chloro-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. Recommanded Product: 1-Chloro-4-methoxybenzene

General procedure: A Schlenk flask was charged with aryl chlorides (0.20 mmol), arylboronic acids (0.30 mmol), N-heterocyclic carbenepalladium(II) complex 3 (2 mol %), KOtBu (2.0 equiv), iPrOH(1 mL) and H2O (1 mL). The mixture was stirred at 80 C for 15 h under N2. After cooling, the reaction mixture was evaporated andthe product was isolated by preparative TLC on silica gel plates. The purified products were identified by 1H NMR spectra and their analytical data are given in Supporting Information.

The synthetic route of 1-Chloro-4-methoxybenzene has been constantly updated, and we look forward to future research findings.

Reference:
Article; Wang, Tao; Xie, Huanping; Liu, Lantao; Zhao, Wen-Xian; Journal of Organometallic Chemistry; vol. 804; (2016); p. 73 – 79;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 54788-38-4, These common heterocyclic compound, 54788-38-4, name is 2-Chloro-4-methoxy-1-methylbenzene, 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.

Referecne Example 1; (3-Bromophenyl) (4-chloro-2-hydroxy-5-methylphenyl) methanone; Aluminum chloride (20.4 g) was added to a solution of 3-chloro-4-methylanisole (20 g) in chlorobenzene (56 ml) at 20-30C, and then 3-bromobenzoyl chloride (28 g) was further added dropwise over about 30 minutes at 25 to 30C. After completion of addition, the mixture was stirred at 25C for 1 hour, and then heated at 40C for 1 hour. After the reaction was completed, the mixture was cooled, and toluene/tetrahydrofuran (1: 1,200 ml) was added dropwise at 20 to 30C. Then, 4N hydrochloric acid (80 ml) was added dropwise. The organic layer was separated, washed successively with 2N hydrochloric acid (60 ml) and a 10% aqueous sodium chloride solution. The organic layer was concentrated to 80 g. After methanol (100 ml) was added, the mixture was concentrated again to 90 g. Methanol (80 ml) was added to the residue, the mixture was stirred at room temperature for 30 minutes, and below 5C for 1 hour. Crysatls were collected, washed with cooled methanol (40 ml) and dried under reduced pressure to obtain the title compound (35.4 g, yield 85.1 %). H-NMR (300MHz, CDC13) 5 (ppm): 2.28 (3H, s), 7.12 (1H, s), 7.36-7. 42 (2H, m), 7.54-7. 57 (1H, m), 7.72-7. 80 (2H, m), 11.7 (1H, s).

The synthetic route of 54788-38-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; WO2005/82879; (2005); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 883499-24-9, name is 1-Bromo-2-chloro-3-fluorobenzene, 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 883499-24-9, SDS of cas: 883499-24-9

Under nitrogen environment,And at reflux temperature, 7-(diphenylamino)-9,9′-dimethyl-9H-fluoren-3-ol (100 g),1-bromo-2-chloro-3-fluorobenzene (58.3 g),The flask of potassium carbonate (91.5 g) and NMP (500 ml) was heated and stirred for 4 hours.After the reaction stopped, the reaction solution was cooled to room temperature, and water was added,The precipitate deposited was extracted by suction filtration. Use water in turn,After washing the obtained precipitate with methanol,Refined with silicone tubing (dissolved solution: toluene),Thus, 6-(3-bromo-2-chlorophenoxy)-9,9-dimethyl-N,N-diphenyl-9H-fluoren-2-amine (150 g) was obtained.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Bromo-2-chloro-3-fluorobenzene, and friends who are interested can also refer to it.

Reference:
Patent; KWANSEI GAKUIN EDUCATIONAL FOUNDATION; JNC CORPORATION; HATAKEYAMA, TAKUJI; MASUDA, KATSUYA; YAMAGA, YUKO; YANAI, MOTOKI; (214 pag.)TW2019/4977; (2019); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 87851-77-2, The chemical industry reduces the impact on the environment during synthesis 87851-77-2, name is O-(3-Chloroallyl)hydroxylamine, I believe this compound will play a more active role in future production and life.

d) 2-(1-((E)-3-Chloro-2-propenyloxyimino)propyl)-5-(3,7-dioxabicyclo[4.1.0]hept-6-yl)-3-hydroxycyclohex-2-enone 7.9 g (29.5 mmol) of 2-(1-oxopropyl)-5-(3,7-dioxabicyclo[4.1.0]-hept-6-yl)-3-hydroxycyclohex-2-enone in 20 ml of methanol were mixed at room temperature with 3.5 g (32.4 mmol) of O-((E)-3-chloro-2-propenyl)hydroxylamine, and the mixture was stirred for about 10 hours. Concentration under reduced pressure gave an oil in quantitative yield which could be purified by chromatography over silica gel using cyclohexane/ethyl acetate. Yield 6.6 g. 1 H NMR (CDCl3): delta=1.13 (t); 1.93 (m); 2.20-2.75 (m); 2.90 (m); 3.13 (m); 3.50 (m); 3.98 (m); 4.52 (d); 6.10 (m); 6.35 (d); 14.3 (s).

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, O-(3-Chloroallyl)hydroxylamine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BASF Aktiengesellschaft; US6107254; (2000); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 220227-21-4,Some common heterocyclic compound, 220227-21-4, name is 2,4,5-Trifluorobenzene-1-sulfonyl chloride, molecular formula is C6H2ClF3O2S, 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.

Intermediate 19 1,1 -dimethylethyl (2S,4R)-2-methyl-4-{[(2,4,5-trifluorophenyl)sulfonyl]amino}-1- pyrrolidinecarboxylateTo 1 ,1-dimethylethyl (2S,4R)-4-amino-2-methyl-1-pyrrolidinecarboxylate (0.075 g, 0.38 mmol) in DCM (~5 mL) was added a solution of 2,4,5-trifluorobenzenesulfonyl chloride (0.075 g, 0.38 mmol) in DCM (~5 mL) and DIPEA (0.13 mL, 0.75 mmol). The resultant mixture was stirred at room temperature overnight, evaporated and loaded onto a 5 g silica SPE cartridge, eluting sequentially with DCM and ethyl acetate. The ethyl acetate fractions were combined and evaporated to afford the title compound (0.0942 g). LC-MS: m/z, 395 (M+H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2,4,5-Trifluorobenzene-1-sulfonyl chloride, its application will become more common.

Reference:
Patent; GLAXO GROUP LIMITED; WO2009/26197; (2009); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Related Products of 452-83-5, 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. 452-83-5 name is 2-Chloro-5-fluoroaniline, 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.

General procedure: NaOt-Bu (0.240 g, 2.5 mmol), Pd(OAc)2 (0.006 g, 0.025 mmol) and [HPt-Bu3][BF4] (0.010 g, 0.035 mmol) were suspended in toluene (3 ml) in a 5 ml microwave vial. The appropriate 2-chloroaniline (0.50 mmol) and aryl bromide (0.50 mmol) were then added and the vial sealed. The reaction was then heated in the microwave reactor at 160 C for 3 h, allowed to cool, and then quenched by addition of aqueous HCl (2 M, 3 ml). The organic phase was extracted with CH2Cl2 (2×20 ml), dried (MgSO4), then filtered and the solvent removed under reduced pressure. The crude product mixture was then subjected to column chromatography (SiO2).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Chloro-5-fluoroaniline, and friends who are interested can also refer to it.

Reference:
Article; Bedford, Robin B.; Bowen, John G.; Weeks, Amanda L.; Tetrahedron; vol. 69; 22; (2013); p. 4389 – 4394;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 118-69-4, name is 2,6-Dichlorotoluene, 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 118-69-4, Quality Control of 2,6-Dichlorotoluene

To a 25 mL reaction flask was added 1,3-diphenylpropanedione iron (0.025 mmol) in turn,Ferrous phthalocyanine (0.0025 mmol),Triethoxy carveda (1.5 mmol)Sodium persulfate (0.75 mmol),(L · 25 mmol), acetone (lmL), water (lmL), and the reaction mixture was reacted at 80 C for 17 h. The reaction was terminated with the addition of aqueous ammonia (2 mL) to remove the polymethylhydrogensiloxane, 10 mL of saturated brine was added and extracted with ether (10 mL X3). The organic phases were combined and the solvent was evaporated under reduced pressure.To 60% yield.

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; Nanjing Normal University; Han Wei; Zhao Hongyuan; (14 pag.)CN107216242; (2017); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 2106-04-9,Some common heterocyclic compound, 2106-04-9, name is 3-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.

Example 1 (4S)-4- ({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}oxy)-N- cyclopropyl-1-methyl-D-prolinamide Example 1 HATU (0.23g) was added to an agitated solution of (4Y)-4- ( {4- [ (3-CHLORO-2- fluorophenyl) AMINO]-7-METHOXYQUINAZOLIN-6-YL} OXY)-1-METHYL-D-PROLINE (7) (0.18g), cyclopropylamine (34.4mg) and DIPEA (156mg) IN METHYLENE CHLORIDE (5M1). After 16hrs the reaction mixture was reduced in vacuo. The residues were re-dissolved in methylene chloride and washed with sodium hydroxide solution (2M) and water. The organic phase was then purified by column chromatography on silica eluting with increasingly polar mixtures of METHANOL/METHYLENE CHLORIDE (0/100-10/90). THE fractions containing the desired product were combined and evaporated to a foam which was triturated with diethylether to give the title compound as a white solid. (0. 15G). LH NMR Spectrum : (DMSO d6) 0.40-0. 48 (m, 2H), 0.57-0. 64 (M, 2H), 2.05-2. 14 (M, 1H), 2.28 (s, 3H), 2.33-2. 45 (M, 1H), 2.48-2. 56 (M, 1H + DMSO), 2. 61-2. 70 (M, 1H), 3.08 (t, 1H), 3.64 (dd, 1H), 3.94 (s, 3H), 5.06 (M, 1H), 7.20 (s, 1H), 7.28 (t, 1H), 7.44-7. 56 (M, 2H), 7.65 (s, 1H), 7.87 (d, 1H), 8.35 (s, 1H), 9.63 (s, 1H); Mass SPECTRUM : (M+H) + 486. 44 The starting material 1, 2-PYRROLIDINEDICARBOXYLIC acid, 4-hydroxy-, 1- (1, 1-DIMETHYLETHYL) 2- methyl ester, (2R, 4R) (2) was prepared as follows: 1- [3- (DIMETHYLAMINO) PROPYL]-3-ETLIYLCARBODIIMIDE hydrochloride (14.73 g) was added to a stirred suspension of 1, 2-PYRROLIDINEDICARBOXYLIC acid, 4-hydroxy-, l- (l, l-dimethylethyl) ester, (2R, 4R) (1) (13.65 g), DIMETHYLAMINOPYRIDINE (21.65 g) and methanol (5.67 g) in methylene chloride (400 ml) and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was washed with citric acid (1.0 M), saturated aqueous sodium bicarbonate solution and saturated brine, dried over MgSO4, filtered and evaporated. The residues were then purified by column chromatography on silica eluting with increasingly polar mixtures of METHANOL/METHYLENE chloride (1/99-5/95). The desired product fractions were combined and evaporated to give 1, 2-PYNOLIDINEDICARBOXYLIC acid, 4-hydroxy-, L- (L, L-DIMETHYLETHYL) 2- methyl ester, (2R, 4R) (2) as a white crystalline solid, (5.9 g). 1H NMR Spectrum : (DMSO d6) 1.32 + 1.38 (2s, 9H), 1.76-1. 87 (M, 1H), 2.24-2. 28 (M, 1H), 3.06-3. 15 (M, 1H), 3.42- 3. 51 (m, 1H), 3.60 + 3.63 (2s, 3H), 4.15-4. 24 (M, 2H), 4.92-5. 00 (M, 1H). Starting material 1, 2-Pyrrolidinedicarboxylic acid, 4-hydroxy-1- (1, 1-dimethylethyl) ester, (2R, 4R), (1), (Boc-D-cis-hyp-OH) is commercially available Starting material (3) was prepared as follows: 6-Acetoxy-4-chloro-7-methoxyquinazoline, (Example 25-5 of in W001/66099 ; 10. 0g, 39.6 MMOLE) was added in portions to a stirred 7N methanolic ammonia solution (220 ML) cooled to 10C in an ice/water bath. After stirring for one hour the precipitate was filtered, washed with diethylether and dried thoroughly under high vacuum to give 4-chloro-7- METHOXYQUINAZOLIN-6-OL (3) (5.65g, 67.8%) ; 1H NMR Spectrum : (DMSO d6) 3.96 (s, 3H); 7.25 (s, 1H); 7.31 (s, 1H); 8.68 (s, 1H) ; Mass Spectrum: (M+H) + 211. The starting material (4) was prepared as follows: Di-ethyl azodicarboxylate (5.71g) was added slowly to a stirred suspension of 1,2- PYNOLIDINEDICARBOXYLIC acid, 4-hydroxy-, L- (L, L-DIMETHYLETHYL) 2-methyl ester, (2R, 4R) (2) (5.9g), 4-CHLORO-7-METHOXYQUINAZOLIN-6-OL (3) (4.6g) AND TRIPHENYLPHOSPHINE (8.6g) in methylene chloride (400 ML) at 25C under an atmosphere of nitrogen and the reaction mixture was stirred for 2 hours. The reaction mixture was then evaporated to ½ volume and purified by column chromatography on silica eluting with increasingly polar mixtures of METHANOL/METHYLENE chloride (1/99-3/97). The desired product fractions were combined and evaporated to give 1-tert-butyl 2-methyl (2R, 4S)-4-[(4-chloro-7-methoxyquinazolin-6- yl) oxy] pyrrolidine-1, 2-dicarboxylate (4) as a pale yellow gum. This was used in the preparation of (5) without further purification. The starting material methyl (4S)-4-({4-[(3-CHLORO-2-FLUOROPHENYL) AMINO]-7- METHOXYQUINAZOLIN-6-YL} OXY)-D-PROLINATE HYDROCHLORIDE (5) was prepared as follows: 4. 0M HCl in Dioxane (15 ml) was added to a suspension of 1-tert-butyl 2-methyl (2R, 4S)-4- [(4-chloro-7-methoxyquinazolin-6-yl0 oxy] pyrrolidine-1, 2-dicarboxylate (4) AND 3-CHLORO-2- fluoroaniline (2.89g) in acetonitrile (400 ML) and the reaction mixture was stirred and heated at 70C for 3 hours. The resulting precipitate was filtered hot and washed with acetonitrile and diethylether and dried under vacuum to give methyl (4S)-4- (14- [ (3-CLILORO-2- FLUOROPHENYL) AMINO]-7-METHOXYQUINAZOLIN-6-YL} OXY)-D-PROLINATE HYDROCHLORIDE (S) as an off- white solid, (6. 3G). TH NMR Spectrum : (DMSO D6) 2.46-2. 60 (M, 2H), 3.37-3. 46 (M, 1H), 3.71 (s, 3H), 3.89-3. 98 (m, 4H), 4.53 (t, 1H), 5.42 (M, 1H), 7.29 (t, 1H), 7.38-7. 48 (M, 2H), 7.55 (t, 1H), 8.64 (s, 1H), 8.75 (s, 1H)…

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Chloro-2-fluoroaniline, its application will become more common.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2005/30757; (2005); 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 63624-28-2 as follows. Product Details of 63624-28-2

Example 199; 1 -(2,4-Dimethoxybenzensulfonyl)-2-oxo-3-{2-oxo-1 -phenyl-2-[(S)-3-(4- propylpiperazin-1 -yl)pyrrolidin-1 -yl]ethyl}-2,3-dihydro-1 H-benzimidazole-5- carbonitrile; To a solution of 2-oxo-3-{2-oxo-1-phenyl-2-[(S)-3-(4-propyl-piperazin-1-yl)-pyrrolidin- 1-yl]-ethyl}-2,3-dihydro-1 H-benzoimidazole-5-carbonitrile (32 mg, 0.07 mmol), triethylamine (0.02 ml_, 0.13 mmol) and DMAP (catalytic amount) in CH2CI2 (2 ml.) 2,4-dimethoxybenzenesulfonyl chloride (17 mg, 0.077 mmol) was added. The reaction mixture was stirred at room temperature for 24 hours, diluted with water and extracted the aqueous phase with CH2CI2 (3 x). The combined organic phase was washed with saturated NaHCO3 aqueous solution, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography in silica gel using 4% methanol in CH2CI2 as eluent to afford 1-(2,4-dimethoxy- benzenesulfonyl)-2-oxo-3-{2-oxo-1-phenyl-2-[(S)-3-(4-propyl-piperazin-1-yl)- pyrrolidin-1-yl]ethyl}-2,3-dihydro-1 H-benzoimidazole-5-carbonitrile (29 mg, 66%) as a white solid. 1H-NMR (400 MHz, CDCI3): delta 0.88-0.94 (m, 3H), 1.28 (m, 2H), 1.84 (m, 1 H), 2.14 (m, 1 H), 2.25-2.59 (m, 9H), 2.79-3.12 (m, 2H), 3.23-3.58 (m, 2H), 3.48 (s, 3H), 3.73- 3.99 (m, 2H), 3.89 (s, 3H), 6.36-6.44 (m, 2H), 6.65 (d, 8.9 Hz, 1 H), 7.00-7.10 (m, 1 H), 7.22-7.26 (m, 2H), 7.34-7.39 (m, 4H), 7.94 (d, 8.5 Hz, 1 H), 8.14 (d, 8.9 Hz, 1 H). MS (API-ES, pos) m/z = 673

According to the analysis of related databases, 63624-28-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ABBOTT GMBH & CO. KG; WO2008/25736; (2008); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics