Month: September 2021

Synthetic Route of 928783-85-1, These common heterocyclic compound, 928783-85-1, name is 1-Bromo-3-chloro-5-(trifluoromethyl)benzene, 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.

In a 25 mL sealed tube, sodium 2-methylpropan-2-olate (62.7 mg, 653 muetaiotaomicron, Eq: 1.20), bis(dibenzylideneacetone)palladium (31.3 mg, 54.4 muetaiotaomicron, Eq: 0.1) and 2-di-tert-butyl(2′,4′,6′- triisopropylbiphenyl-2-yl)phosphine (23.1 mg, 54.4 muetaiotaomicron, Eq: 0.1) were combined with toluene (5.00 mL) to give a dark brown suspension. N5,N5,l-tris(4-methoxybenzyl)-lH-l,2,4-triazole- 3,5-diamine (250 mg, 544 muetaiotaomicron, Eq: 1.00) and l-bromo-3-chloro-5-(trifluoromethyl)benzene (141 mg, 544 muetaiotaomicron, Eq: 1.00) were added. The reaction mixture was degassed with argon for 15 min, and then heated to 110C for 3 hours. The reaction mixture was cooled and diluted with EtOAc (50 mL), washed with H20 (25 mL) and brine (25 mL). The organic layer was dried over anhydrous MgS04, filtered and volatiles were removed under reduced pressure to yield an oil from which the compound was isolated by column chromatography (Hexanes/EtOAc = 70/30) to give an off-white solid 40 mg (12%). MH+ 638.4

Statistics shows that 1-Bromo-3-chloro-5-(trifluoromethyl)benzene is playing an increasingly important role. we look forward to future research findings about 928783-85-1.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; BILOTTA, Joseph Anthony; CHEN, Zhi; CHIN, Elbert; DING, Qingjie; ERICKSON, Shawn David; GABRIEL, Stephen Deems; KLUMPP, Klaus; MA, Han; MERTZ, Eric; PLANCHER, Jean-Marc; WEIKERT, Robert James; WO2014/6066; (2014); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Electric Literature of 93-50-5, 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. 93-50-5, name is 4-Chloro-2-methoxyaniline, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of 6,8-dichloro-4-oxo-chromene-2-carboxylic acid (Int-2, 1.3 g, 5.02 mmol) in DCM (20 mL) was added 4-chloro-2-methoxyaniline (949 mg, 6.02 mmol), DIPEA (1.15 g, 8.9 mmol) and HATU (3.3 g, 8.9 mmol) at room temperature and the resulting mixture was then stirred at room temperature for 18 hours. After the reaction was completed, the mixture was diluted with water (30 mL) and extracted with EtOAc (50 mL) three times. The combined organic layer was washed with brine, dried over anhydrous Na2S04 and concentrated in vacuo. The residue was purified by silica gel flash chromatography (elution with PE/EtOAc=lO: 1-1:4) to give 6,8-dichloro-N-(4-chloro-2-methoxyphenyl)-4-oxo-chromene-2-carboxamide (1.6 g, 80 %) as a yellow solid. MS obsd. (ESP) [(M+H)+]: 398.1.

The chemical industry reduces the impact on the environment during synthesis 4-Chloro-2-methoxyaniline. I believe this compound will play a more active role in future production and life.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; FENG, Song; LIANG, Chungen; LIU, Yongfu; TAN, Xuefei; WU, Jun; WANG, Jianping; (134 pag.)WO2020/79106; (2020); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 14862-52-3, 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. 14862-52-3 name is 3,5-Dibromochlorobenzene, 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.

Synthesis of compound (1-1) Intermediate (A-1): Synthesis of N^N’.N’-Tetrakis-biphenyl^-yl-S- chloro-benzene-1,3-diamine Tri-ieri-butylphosphine (11.1 mL of a 1.0 M solution in toluene, 11.1 mmol), palladium acetate (1.25 g, 5.55 mmol) and cesium carbonate (75.0 g, 232 mmol) are added to a solution of bis-biphenyl-4-yl-amine (CAS Nr. 102113- 98-4) (59.0 g, 185 mmol) and ,3-Dibromo-5-chloro-benzene (25 g, 92 mol) in degassed toluene (600 ml), and the mixture is heated under reflux for 2 h. The reaction mixture is cooled to room temperature, extended with toluene and filtered through Celite. The filtrate is evaporated in vacuo, and the residue is crystallised from heptane/toluene. Yield: 67.7g, 75%.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3,5-Dibromochlorobenzene, and friends who are interested can also refer to it.

Reference:
Patent; MERCK PATENT GMBH; MUJICA-FERNAUD, Teresa; MONTENEGRO, Elvira; PFISTER, Jochen; (103 pag.)WO2016/78738; (2016); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 1939-99-7, name is Phenylmethanesulfonyl chloride, 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 1939-99-7, Application In Synthesis of Phenylmethanesulfonyl chloride

K2CO3 (8.7 g, 62 mmol) was added into a mixture of phenylmethanesulfonyl chloride (6 g, 31 mmol) and 2-bromoethanamine hydrobromide (6.4 g, 31 mmol) in DCM (100 mL) at 0 C. And the resulting mixture was stirred at r.t. for 4 hours and left standing overnight. Upon the completion of reaction, water (100 mL) was added in and DCM phase was separated. The aqueous phase was extracted with DCM. The combined organic phase was dried over Na2SO4, filtered and concentrated in vacuo to provide a crude which was separated with column chromatography (silica gel with 200-300 mesh, 0 to 50% of EtOAc in petroleum ether) to provide compound N-(2-bromoethyl)(phenyl)methanesulfonamide (7.0 g, 80%) as a pale yellow solid. 1H NMR (300 MHz, CDCl3) delta 7.40 (m, 5H), 4.58 (m, 1H), 4.29 (s, 2H), 3.34-3.29 (m, 4H). LCMS (ESI), 300, 302 [M+Na]+, Br pattern found.

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; Genentech, Inc.; Fauber, Benjamin; Gobbi, Alberto; Rene, Olivier; Bodil van Niel, Monique; Gancia, Emanuela; Gaines, Simon; Laddywahetty, Tammy; Vesey, David; Ward, Stuart; Winship, Paul; US2015/197529; (2015); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Some common heterocyclic compound, 918538-05-3, name is 2,4-Dichloropyrrolo[2,1-f][1,2,4]triazine, molecular formula is C6H3Cl2N3, 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. Product Details of 918538-05-3

To stirred solution of pyridin-4-ylmethanamine (0.086 g, 0.798 mmol) in dioxane (5 mL) was dropwise added DIPEA (0.279 mL, 1.596 mmol) and stirred for 15 mm at room temperature. To the resulting reaction mixture was added 2,4-dichloropyrrolo[2,1- J][1,2,4]triazine (0.15 g, 0.798 mmol) stirred at room temperature for 1 h. The reactionwas monitored by LC-MS. The reaction mixture was concentrated under reduced pressure. To the residue was added water (50 mL) and extracted with ethyl acetate (3×80 mL). The combined organic phase was dried over anhydrous sodium sulfate filteredevaporated. The resulting crude product was purified by silica gel flash chromatography (ethyl acetate/petroleum ether) to get 2-chloro-N-(pyridin-4-ylmethyl)pyrrolo[2, 1-J][1,2,4]triazin-4-amine (0.14 g, 0.5 18 mmol, 64.9 % yield) as a brown solid. LCMS260.0 (M+H); rt 1.8 mm; Conditions E. ?HNMR: (300 MHz, DMSO-d6) oe 9.37-9.28 (m, 1H), 8.58-8.48 (m, 2H), 7.70 (dd, J2.6, 1.5 Hz, 1H), 7.38-7.30 (m, 2H), 7.03 (dd, J4.5, 1.5 Hz, 1H), 6.67 (dd, J4.2, 2.6 Hz, 1H), 4.75 (d, J6.0 Hz, 2H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 918538-05-3, its application will become more common.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; HARIKRISHNAN, Lalgudi S.; FINK, Brian E.; BORZILLERI, Robert M.; TONUKUNURU, Gopikishan; RAHAMAN, Hasibur; WARRIER, Jayakumar Sankara; SESHADRI, Balaji; (411 pag.)WO2017/15425; (2017); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 33786-89-9,Some common heterocyclic compound, 33786-89-9, name is 5-Chloro-m-phenylenediamine, molecular formula is C6H7ClN2, 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.

[3]: 1.1-(4-Methoxyphenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid (500 mg, 1.75 mmol, 1 equiv) was dissolved in .5 mL dry DMF under inert atmosphere with HATU (732 mg, 1.93 mmol, 1.1 equiv). While stirring, DIPEA (1.8 g, 14 mmol, 8 equiv) was added drop wise at 0 C. When all the DIPEA was added, it was allowed to sit for 15 minutes. After this, 5-chloro-m-phenylenediamine (996 mg, 7.0 mmol, 4 equiv) was added. The reaction was allowed to warm up to R.T. over the course of 2 hrs and was monitored by TLC and LC/MS. When complete, 5 mL of H2O and 5 mL of EtOAc were added and the mixture transferred to a seperatory funnel. The aqueous layer was extracted into EtOAc (5 mL X 3). The crude product was dissolved in 1 : 1 ACN : H2O, separated by RP-HPLC (H2O [.1% TFA] : ACN [.1% TFA]), and lyophilized to afford the coupled intermediate as a clear oil (410.78 g/mol, 245 mg, 34% yield).2. A portion of the purified product from step one (100 mg, .22 mmol, 1 equiv) was dissolved in .5 mL dry DMF under inert atmosphere. Dry TEA (90 mg, .85 mmole, 4 equiv) was added via syringe at 0 C.20 mL of acryloyl chloride was transferred via syringe to the reaction vial (22 mg, .242 mmol, 1.1 equiv) at 0 C. The reaction was allowed to warm up to R. T. and was monitored by TLC and LC/MS. Once complete, 1 mL of saturated NaHCO3 solution was added and allowed to mix for 15 minutes to quench the reaction. To this, 5 mL of EtOAc was added and the mixture was transferred to a seperatory funnel. The aqueous layer was extracted into EtOAc (5 mL X 3). The crude product was dissolved in 1 : 1 ACN : H2O, separated by RP-HPLC (H2O [.1% TFA] : ACN [.1% TFA]), and lyophilized to afford compound 3 as a clear oil (464.78 g/mol, 48 mg, 47% yield).1H (500 MHz, (CD3)2SO) d: 10.71 (s, 1H), 10.41 (s, 1H), 8.05 (m, 1H), 7.69 (m, 1H), 7.49 (m, 1H), 8.29 (s, 1H), 7.46 (m, 2H), 7.12 (m, 2H), 6.44(dd, J1 = 17.00Hz, J2= 10.08 Hz, 1H), 6.30(dd, J1 = 17.00 Hz, J2= 1.76Hz, 1H), 5.80(dd, J1 = 10.08 Hz, J2= 1.76Hz, 1H), 3.85(s, 3H).13C (125 MHz, (CD3)2SO) d: 163.47, 160.15, 159.32, 140.64, 140.25, 139.55, 133.08, 131.51, 131.46, 127.64, 127.47 (2C), 120.74, 120.38, 118.22, 114.40 (2C), 114.28, 114.26, 108.83, 55.60.; [4]: 1. Please refer to step one of the synthesis of compound 3 above.2. A portion of the purified coupled intermediate from step one compound 3?s synthesis (100 mg, .22 mmol, 1 equiv) was dissolved in .5 mL dry DMF under inert atmosphere. Dry TEA (90 mg, .85 mmole, 4 equiv) was added via syringe at 00C.20 mL of propionyl chloride was transferred via syringe to the reaction vial (22 mg, .242 mmol, 1.1 equiv) at 00C. The reaction was allowed to warm up to R. T. and was monitored by TLC and LC/MS. Once complete, 1 mL of saturated NaHCO3 solution was added and allowed to mix for 15 minutes to quench the reaction. To this, 5 mL of EtOAc was added and the mixture was transferred to a seperatory funnel. The aqueous layer was extracted into EtOAc (5 mL X 3). The crude product was dissolved in 1 : 1 ACN : H2O, separated by RP-HPLC (H2O [.1% TFA] : ACN [.1% TFA]), and lyophilized to afford compound 4 as a clear oil (466.8 g/mol, 74 mg, 72% yield).1H (500 MHz, (CD3)2SO) d: 10.66 (s, 1H), 10.12 (s, 1H), 8.28, (s, 1H), 7.97 (m, 1H), 7.58 (m, 1H), 7.46 (m, 3H), 7.12 (m, 2H), 3.85 (s, 3H), 2.33 (q, J = 7.6 Hz, 2H), 1.08 (t, J = 7.6 Hz, 3H).13C (125 MHz, (CD3)2SO) d: 172.47, 160.13, 159.29, 140.96, 140.16, 139.54, 132.96, 131.47, 127.47 (2C), 120.78, 120.39, 118.22, 114.40 (2C), 113.97, 113.73, 108.52, 55.60, 29.56, 9.53.

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

Reference:
Patent; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; SHOKAT, Kevan, M.; GENTILE, Daniel; MOSS, Steven; (380 pag.)WO2018/112420; (2018); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

These common heterocyclic compound, 1005-56-7, name is O-Phenyl carbonochloridothioate, 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. Product Details of 1005-56-7

A suspension of activated zinc dust (98.5 mg, 1.51 mmol) and ethyl bromodifluoroacetate (0.19 mL, 1.51 mmol) in THF (5 mL) was refluxed for 20 min and then cooled to 00C. To this, the solution of the aldehyde (+)- 39 (100 mg, 0.30 mmol) in THF (5 mL) was added. The reaction mixture was warmed to15 room temperature, followed by refluxing for 20 min, and then cooled to room temperature. The reaction mixture was poured into 1 M KHSO4 and extracted with EtOAc (3x 20 mL), washed with brine, dried over MgSO4, concentrated in vacuo, and then purified by column chromatography (10% EtOAc/hexanes) to give 84.5 mg (62%) of a 1:1 mixture of diastereomers of the desired alcohol as a colorless oil. To a solution of ethyl ester (84 mg,20 0.18 mmol) and pyridine (0.066 mL, 0.82 mmol) in CH2Cl2 (5 mL), phenyl chlorothionoformate (0.053 mL, 0.38 mmol) was added. After being stirred at room temperature for 20 hours, the reaction mixture was diluted with water, extracted with ether (3x 20 mL), washed with satd NaHCO3 solution and brine, dried over MgSO4, concentrated in vacuo, and then purified by column chromatography (5% EtOAc/hexanes) to give 97.825 mg (90%) of the desired carbonate as diastereomeric mixtures. To the solution of the resulting phenylthianocarbonate (97.5 mg, 0.16 mmol) in anhydrous benzene (10 mL), 2,2′- azobisisobutyronitrile (AlBN, 5 mg) and tributyltin hydride (0.066 mL, 0.24 mmol) were added at room temperature. After being refluxed for 3 hours, the mixture was cooled to 0 0C, diluted with water, extracted with EtOAc (3x 20 mL), washed with brine, dried over30 MgSO4, concentrated in vacuo, and then purified by column chromatography (3%EtOAc/hexanes) to give 58.2 mg (80%) of the desired difluoro ester 42 as a colorless oil: 1H NMR (400 MHz, CDCl3) delta 4.32 (q, J= 7.2 Hz, 2H), 4.03 (s, IH), 2.14-2.06 (m, IH), 1.98- 1.89 (m, 2H), 1.85-1.75 (m, 2H), 1.69-1.64 (m, IH), 1.61-1.53 (m, 2H), 1.49-1.43 (m, EPO IH), 1.38-1.34 (m, 2H), 1.35 (t, J= 7.2 Hz5 3H), 1.26-1.17 (m, 3H), 1.13-0.99 (m, 2H), 0.94 (t, J= 8.0 Hz, 9H), 0.91 (d, J= 6.0 Hz5 3H), 0.90 (s, 3H), 0.55 (q, J= 8.0 Hz, 6H).

The synthetic route of O-Phenyl carbonochloridothioate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JOHNS HOPKINS UNIVERSITY; WO2006/74227; (2006); A2;,
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. 2533-69-9, name is Methyl 2,2,2-trichloroacetimidate belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Safety of Methyl 2,2,2-trichloroacetimidate

General procedure: The thiol was placed in a dry round bottom flask and dissolved in anhydrous THF (or toluene) to a concentration of 0.2 M. The trichloroacetimidate (1.2 equiv) was then added and the reaction was warmed to reflux. After 18 hours the reaction was cooled to room temperature and concentrated under reduced pressure. The residue was then pre-adsorbed on silica gel and purified by column chromatography. Alternatively, the residue can be dissolved in ethyl acetate, washed with 2M aq. NaOH(3x), dried (Na2SO4) and concentrated (this workup removes the trichloroacetamide byproduct). Forsome sulfides this workup provided analytically pure material, in others the residue is purified by silicagel chromatography to provide the pure sulfide product.

The synthetic route of 2533-69-9 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Duffy, Brian C.; Howard, Kyle T.; Chisholm, John D.; Tetrahedron Letters; vol. 56; 23; (2015); p. 3301 – 3305;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 95-51-2, These common heterocyclic compound, 95-51-2, name is 2-Chloroaniline, 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.

(I) in the reaction container by adding O-aminochlorobenzene 0.8mol, aqueous solution 100 ml, control the stirring speed in the 500rpm, by adding the mass fraction is 60% of sodium bromide solution 300 ml, control the temperature of the solution to 9 C, potassium sulfite dropping 0.8mol dissolved in 120 ml of an aqueous solution, keeping the temperature of the solution after the added in 40 C, time-keeping 3h, potassium iodide test for determining the end point of the reaction, the diazonium salt is generated (3);(Ii) taking stannous chloride 0.12mol, the mass fraction of 70% sodium bromide solution of 300 ml mixed in the reaction vessel, heating the solution temperature to 92 C, dropping step (i) generating the diazotizing solution, maintaining the temperature of the solution is in the 95 C, after adding water vapor distillation, oil-free object until the distillate, separating the organic layer, the aqueous layer extracted with ethanol solvent 7 time, combined with the extracted oil, are sequentially used for quality score for the 30 […] 40% phosphoric acid washing, potassium bicarbonate solution, the mass fraction of 10% – 20% of the potassium bromide solution, phosphorus pentoxide dehydration, to extracting distilled 1.3kPa vacuum distillation, collecting 180 – – 185 C fraction, O-chloro-bromobenzene may be colorless transparent product 143.63g, yield 94%.

Statistics shows that 2-Chloroaniline is playing an increasingly important role. we look forward to future research findings about 95-51-2.

Reference:
Patent; Chengdu Railway Technology Co., Ltd. Henghua; Peng, Xiangliang; (4 pag.)CN105541545; (2016); A;,
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. 1005-56-7, name is O-Phenyl carbonochloridothioate, This compound has unique chemical properties. The synthetic route is as follows., Application In Synthesis of O-Phenyl carbonochloridothioate

194.2 mg (1.0 mmol) of methyl alpha-D-glucopyranoside, 41.6 mg (0.10 mmol) of dioctyl dichloro tin, tetrabutylammonium iodide36.9 mg (0.10 mmol) and 10 ml of tetrahydrofuran were added and stirred. To this mixed solution, 0.175 ml (1.3 mmol) of phenyl chlorothionoformate was added, then 0.271 ml (1.5 mmol) of 1,2,2,6,6-pentamethylpiperidine was added and the mixture was stirred at 20 C. for 6 hours.After completion of the reaction, 20 ml of a saturated aqueous solution of ammonium chloride was added to the reaction solution, and extraction operation was carried out three times with 20 ml of ethyl acetate. The organic phase (ethyl acetate phase) was washed with 20 ml of water and 20 ml of an aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and the solvent (ethyl acetate) was distilled off under reduced pressure. The residue was purified by silica gel chromatography (developing solvent n-hexane: ethyl acetate = 5:: 1), 319.5 mg (yield: 97%) of methyl 2-O-phenoxythiocarbonyl-alpha-D-glucopyranoside was obtained.

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 1005-56-7.

Reference:
Patent; NAGASAKI UNIVERSITY; TOKUYAMA CORPORATION; ONOMURA, OSAMU; MURAMATSU, WATARU; TANIGAWA, SATOKO; IWASAKI, FUMIAKI; (19 pag.)JP5669637; (2015); B2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics