Month: February 2021

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 101-55-3 as follows. HPLC of Formula: C12H9BrO

(1) Grignard reagent: first in a 1000mL three-necked flask, Add 600mLTHF and 200g 4 – Bromodiphenyl ether stirred solution, spare. Then in a 2000mL three-necked flask was added 21.5g of magnesium, 20 mL THF, one small Iodine, 20mL of prepared 4-bromo-diphenyl ether in THF was added dropwise, and after the initiation of heating, the remaining 4-bromo-diphenyl ether in THF was added dropwise at 30-35 C. After the addition, the mixture was incubated at 30-35 C Stirred for 1 hour, The flask was cooled to -30 C with liquid nitrogen until ready for use. (2) Borated: In the above format liquid, 100.1 g of trimethyl borate 600 mL THF solution was slowly added dropwise, Dropping process to maintain -40 ~ -30 the following, After dropping the mixture was allowed to warm to room temperature, 400 ml of 10% hydrochloric acid was added dropwise and refluxed for 1 hour. After distilling off the THF, 500 ml of cold water was added and the mixture was stirred for 30 minutes, cooled, crystallized and separated, 154.1 g of 4-phenoxybenzeneboronic acid were obtained, The yield is 90%. (3) Purification: In a 1 L three-necked flask were added 154.1 g of wet crude 4-phenoxybenzeneboronic acid, Add 200 mL of toluene to dissolve, desolvate, cool, crystallize and centrifuge to obtain 137 g of 4-phenoxybenzeneboronic acid product in a yield of 80%

According to the analysis of related databases, 101-55-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Bengbu Zhong Shi Chemical Co., Ltd.; Yang Qing; Liu Hongqiang; Zhao Shimin; Xu Jianxiao; (5 pag.)CN105820184; (2016); A;,
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Some common heterocyclic compound, 5961-59-1, name is 4-Methoxy-N-methylaniline, molecular formula is C8H11NO, 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: 4-Methoxy-N-methylaniline

HATU (1.5 g, 4.0 mmol) was added to a stirred solution of 4-methoxy-N-methylaniline mg, 3.64 mmol) and (S)-2-((tert-butoxycarbonyl)amino)-3-phenylpropanoic acid (1.06 g, 4.0 mmol) in DMF (20 mL) and DIPEA (1.3 mL, 7.3 mmol) and the reaction mixture was stirred at rt for 4h. The reaction was concentrated and the residual crude oil was partitioned between EtOAc (-60 mL) and 1/2 sat. NaHCC (aq) (-60 mL). The organic component was washed with brine (-40 mL), dried (MgS04), filtered, concentrated and purified using a Biotage Horizon (80 g SiC , 10-40% EtOAc/hexanes) to yield Intermediate JB-1 (1.34 g) as a clear amber viscous oil. LC-MS retention time = 3.17 min; m/z = 385.3 [M+H]+. (Column: Phenonenex-Luna C18 2.0 x 50mm 3 muiotaeta. Solvent A = 95% Water:5% Acetonitrile: 10 mM NH4OAc. Solvent B = 5% Water:95% Acetonitrile: 10 mM NH4OAc. Flow Rate = 0.8 mL/min. Start % B = 0. Final % B = 100. Gradient Time = 4 min. Wavelength = 220). NMR (400 MHz, CDCh) delta 7.25 – 7.20 (m, 3H), 7.03 – 6.64 (m, 6H), 5.20 (d, J=8.8 Hz, 1H), 4.53 (app q, J=7.4 Hz, 1H), 3.83 (s, 3H), 3.18 (s, 3H), 2.89 (dd, J=13.1, 7.5 Hz, 1H), 2.71 (dd, J=13.1, 6.5 Hz, 1H), 1.39 (s, 9H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5961-59-1, its application will become more common.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; BENDER, John A.; GENTLES, Robert G.; PENDRI, Annapurna; WANG, Alan Xiangdong; MEANWELL, Nicholas A.; BENO, Brett R.; FRIDELL, Robert A.; BELEMA, Makonen; NGUYEN, Van N.; YANG, Zhong; WANG, Gan; KUMARAVEL, Selvakumar; THANGATHIRUPATHY, Srinivasan; BORA, Rajesh Onkardas; HOLEHATTI, Shilpa Maheshwarappa; METTU, Mallikarjuna Rao; PANDA, Manoranjan; (319 pag.)WO2016/172424; (2016); A1;,
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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 53087-13-1 as follows. HPLC of Formula: C13H11BrO

1.85 g of magnesium was suspended in 15 ML of diethyl ether, to which a catalytic amount of iodine was added and then a solution of 20.00 g of 1-(benzyloxy)-3-bromobenzene in 40 ML of diethyl ether was added dropwise and this mixture was stirred for 8 hours while heating it under reflux.. The reaction mixture was cooled to 5C, to which a solution of 6.72 ML of cyclopentanone in 20 ML of diethyl ether was added dropwise, and this mixture was stirred for one hour at room temperature.. Then an aqueous solution of ammonia chloride was added to the ice-cooled reaction mixture, and the organic phase was separated therefrom.. After the resultant organic phase was washed with water and a saturated sodium chloride solution successively, the washed phase was dried over anhydrous magnesium sulfate, and the solvent was distilled out under reduced pressure.. The resultant residue was purified by silica gel column chromatography [eluent; hexane:ethyl acetate=10:1] to yield 7.65 g of 1-[3-(benzyloxy)phenyl] cyclopentanol as yellow oil. NMR(400MHz,CDCl3) delta value: 1.52(1H,s), 1.79-1.88(2H,m), 1.93-2.04(6H,m), 5.08(2H,s), 6.85(1H,ddd,J=8.4,2.8,1.2Hz), 7.08(1H,ddd,J=7.6,1.6,0.8Hz), 7.16-7.17(1H,m), 7.24-7.46(6H,m)

According to the analysis of related databases, 53087-13-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; TOYAMA CHEMICAL CO., LTD.; Hirono, Shuichi; Shiozawa, Shunichi; EP1445249; (2004); A1;,
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Adding a certain compound to certain chemical reactions, such as: 1836-62-0, name is 2-(2-Methoxyphenoxy)ethylamine, belongs to ethers-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 1836-62-0, Recommanded Product: 1836-62-0

2- (2-methoxyphenoxy) ethanamine (851 mg, 5.1 mmol),Benzaldehyde (540 mg, 5.1 mmol),Para-Toluenesulfonic acid (PTSA, 105 mg, 0.55 mmol) was dissolved in 5 mL of toluene.The mixed solution was refluxed, maintained and stirred.TLC (Thin Layer Chromatography) was used to confirm the completion of the reaction, and then the temperature was lowered to room temperature.The mixture was separated using water and ethyl acetate, and washed with a saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulphate and concentrated in vacuo to give crude product.The crude product prepared from the above was dissolved again in methanol (10 ml) at 0 C. Sodium borohydride (250 mg, 6.6 mmol) was slowly added dropwise and the temperature was raised to room temperature. After 24 hours of reaction, the mixture was diluted with dichloromethane and water. The diluted solution was extracted, separated and washed with a saturated aqueous sodium chloride solution three times. It was then dried over magnesium sulfate, concentrated in vacuo, and purified by flash column chromatography on silica gel, 10-50% ethyl acetate / hexane to finally yield the desired compound.

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

Reference:
Patent; Gachon University Industry Academy Cooperation Foundation; Kim Mi-hyeon; Kim Seon-yeo; Jang Cheong-yun; (29 pag.)KR2018/125090; (2018); A;,
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Electric Literature of 583-19-7,Some common heterocyclic compound, 583-19-7, name is 1-Bromo-2-ethoxybenzene, molecular formula is C8H9BrO, 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 V.1 (X1 = Br, X2 = Cl): 1-bromo-2-ethoxybenzene-1-sulfonyl chloride; To a solution of 9 g (45 mmol) of 1-bromo-2-ethoxybenzene (intermediate VI.1) in 220 mL of dichloromethane, a solution of 9 mL (135 mmol) of chlorosulfonic acid in 16 mL of dichloromethane was added for one hour at -5C. Then it was stirred for an additional 1 hour, at room temperature. The reaction mixture was carefully poured over about 500 g of crushed ice and the resulting phases were allowed to decant and were separated. The organic phase was washed, successively, with 220 mL of a 5% Na2CO3 aqueous solution, 220 mL of NaHCO3 saturated aqueous solution, 220 mL of water and 220 mL of brine. Then, it was dried over anhydrous sodium sulfate and evaporated to dryness to obtain 11.91 g (89% yield) of 1-bromo-2-ethoxybenzene-1-sulfonyl chloride as a yellow oil. 1H NMR (CDCl3, 200 MHz) delta (ppm): 8.21 (d, J = 2.2 Hz, 1H); 7.96 (dd, J = 2.2 Hz, J = 9.2 Hz, 1H) ; 7.01 (d, J = 9.2 Hz, 1H); 4.24 (q, J = 7.0 Hz, 2H) ; 1.55 (t, J = 7.0 Hz, 3H).

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

Reference:
Patent; Galenicum Health, S.l.; EP2168967; (2010); A1;,
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Reference of 1116-77-4, These common heterocyclic compound, 1116-77-4, name is 4,4-Diethoxy-N,N-dimethyl-1-butanamine, 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.

(ii) Preparation of crude rizatriptan benzoate; Into a clean IOOL glass reactor were charged water (20L) cone. HCl (8.5L), and l-(4- aminophenylmethyl)-l,2,4-triazole (5.0Kg). The reaction mass was stirred for 20-30min at 25-30 C and cooled to 0-5 C. Aqueous sodium nitrite (2.1Kg in 3.0Lof water) was added to the reaction mass below 5C over a period of 2hr. The reaction mass was maintained below 50C for lhr.Into a clean, 200L glass reactor were charged water (30 L) and sodium sulfite (9.0 Kg) under nitrogen atmosphere at 25-30 C. The resulting solution was cooled to below 10 C. Above diazonium salt solution was added to the reaction mass in 20-30 min period keeping the temperature below 10 C. The reaction mass was slowly heated to 65-7O0C over a period of 2.5-3. Ohr. After maintaining at this temperature for 2hr sulfuric acid EPO (7.2L) was added to the reaction mixture and continued the maintenance at same temperature for 2.0-2.5 hr. The reaction mass was cooled to reach 20-25 0C.4-Dimethylaminobutyraldehyde diethyl acetal (7.8 kg) was added to the reaction mass in 30-45min keeping the temperature at 25-30 C. The reaction mass was maintained at this temperature for 4-5hr. TLC of the reaction mass indicated the absence of starting material. The reaction mass was heated to 35-400C and maintained for lhr. Temperature of the reaction mass was further raised to 60-65C and maintained for 3.5hr. The reaction mass was cooled to 20-30C and adjusted the pH of reaction mass to 6.5-7.0 with ammonia solution. Ethyl acetate (15L) was added to the reaction mass and stirred for 15- 20min and separated the organic layer. Aqueous layer pH was adjusted to 8.5-9.0 with ammonia solution. Aqueous layer was extracted with ethyl acetate (3 x 35L). Combined ethyl acetate layer was treated with activated carbon (lkg) and distilled of solvent under reduced pressure to get 4.7kg crude rizatriptan base as oil.The above crude rizatriptan base was dissolved in 18L of acetone at 25-30 0C. Benzoic acid (2.1kg) was added to the reaction mass at 25-30 C. After stirring for 45-60min at 25-30 C the reaction mixture was cooled to below 0 C and maintained for 10-12hr. The reaction mass was allowed to reach 20-25 0C and maintained for 2.5hr- before filtration. The wet cake was washed with 3.5L of acetone. Drying at 50-60 C gave 3kg of rizatriptan benzoate.; Example 4; Preparation of rizatriptan benzoate; (i) Preparation of crude rizatriptan benzoate:; Into a clean IOOL glass reactor were charged water (30L)5 cone. HCl (15kg), and l-(4- aminophenylmethyl)-l,2,4-triazole (7.5Kg). The reaction mass was stirred for 20-30min at 25-30 0C and cooled to below 0 C. Aqueous sodium nitrite (3.2Kg in 5Lof water) was added to the reaction mass below 5C over a period of 2hr. The reaction mass was maintained below 5C for lhr.Into a clean, 200L glass reactor were charged water (45 L) and sodium sulfite (13.5 Kg) under nitrogen atmosphere at 25-30 C. The resulting solution was cooled to below 10 0C. The above prepared diazonium salt solution was added to the reaction mass in 20-30 min period keeping the temperature below 10 C. The reaction mass was slowly heated to 65-70C over a period of 2.5-3.Ohr. After maintaining at this temperature for 2hr sulfuric acid (19.8kg) was added to the reaction mixture and continued the maintenance at same temperature for 2.0-2.5 hr. The reaction mass was cooled to reach 20-25 0C.4-Dimethylaminobutyraldehyde diethyl acetal (11.7 kg) was added to the reaction mass in 30-45min keeping the temperature at 25-30 0C. The reaction mass was maintained at this temperature for 4-5hr. TLC of the reaction mass indicated the absence of starting material. The reaction mass was heated to 35-40C and maintained for lhr. Temperature of the reaction mass was further raised to 60-65C and maintained for 3.5hr. The reaction mass was cooled to 20-30C and adjusted the pH of reaction mass to 6.5-7.0 with ammonia solution. Ethyl acetate (15L) was added to the reaction mass and stirred for 15-20min and separated the organic layer. Aqueous layer pH was adjusted to 8.8-9.2 with ammonia solution. Aqueous layer was extracted with ethyl acetate (3 x 45L). Combined ethyl acetate layer was treated with activated carbon (1.5kg) and distilled of solvent under reduced pressure to get 7.5kg of crude rizatriptan base as oil. EPO The above crude rizatriptan base was dissolved in 3OL of acetone at 25-30 0C. Benzoic acid (3.5kg) was added to the reaction mass at 25-30 C. After stirring for 45-60min at 25-30 C the reaction mixture was cooled to below 0 C and maintained for 10-12hr. The reaction mass was allowed to reach 20-25 C and maintained for 2.5hr before filtration. The wet cake was washed with 5L of acetone. Drying at 50-60 0C gave 4.5kg of rizatriptan benzoate.

Statistics shows that 4,4-Diethoxy-N,N-dimethyl-1-butanamine is playing an increasingly important role. we look forward to future research findings about 1116-77-4.

Reference:
Patent; NATCO PHARMA LIMITED; PULLA REDDY, Muddasani; SATYASRINIVAS, Hanumara; RADHARANI, Kagitha; VENKAIAH CHOWDARY, Nannapaneni; WO2006/137083; (2006); A1;,
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Electric Literature of 2393-23-9, 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. 2393-23-9, name is 4-Methoxybenzylamine belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To a solution of p-anisaldehyde (146 mmol) in ethanol (500 mL) was added 4- methoxybenzylamine (146 mmol). The mixture was then cooled in an ice water bath. NaBH4 (294 mmol) was added in portions and the reaction mixture was allowed to warm to rt, gradually. Ice water slush (100 mL) was added and the mixture was concentrated to half its original volume. The mixture was then extracted with ether and the organics were combined, washed with brine, dried, and concentrated. Hexane (~50 mL) was added and the precipitate was filtered to give 35 g of bis-(4-methoxy-benzyl)-amine, 19, as white solid.

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

Reference:
Patent; IRM LLC; WO2006/81554; (2006); A2;,
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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. 7252-83-7, name is 2-Bromo-1,1-dimethoxyethane, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 7252-83-7

To an ice cooled solution of sodium ethoxide (3.26 g, 48.0 mmol) in ethanol (25.0 mL) was slowly added 4-methoxybenzenethiol (6.73 g, 48.0 mmol). The reaction mixture was stirred for 15 min. 2-Bromo-l,l-dimethoxyethane (5.64 mL, 48.0 mmol) was added, and the reaction mixture was refluxed for 2 h. After the precipitate was isolated by filtration, the mother liquor was evaporated under reduced pressure. The resultant residue was diluted with diethyl ether (100 mL) and washed with water and brine, dried over sodium sulfate, filtered, and concentrated to give the desired crude product (11.0 g) which was directly used in next step reaction without further purification. 1H-NMR (400 MHz, CDCl3): 7.40 (m, 2H), 6.85 (m, 2H), 4.47 (t, J = 5.6 Hz, IH), 3.80 (s, 3H), 3.34 (s, 6H), 3.01 (d, J = 5.6 Hz, 2H).

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 7252-83-7.

Reference:
Patent; INCYTE CORPORATION; ZHUO, Jincong; METCALF, Brian; WO2008/64157; (2008); A1;,
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Some common heterocyclic compound, 767-91-9, name is 2′-Methoxyphenyl acetylene, molecular formula is C9H8O, 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. COA of Formula: C9H8O

General procedure: To a mixture of alpha-azidoamide 16aa (34 mg, 0.20 mmol) and phenylacetylene (9a; 24 L,0.20 mmol) in t-BuOH/H2O (2 mL, 1:1) were added 0.5 M CuSO4 (0.020 mL, 0.010 mmol) and 1.0 M sodium ascorbate (0.020 mL, 0.020 mmol). The reaction mixture was stirred at room temperature for 1 day, and then the resulting reaction mixture was filtered. The separated solid was washed with H2O and hexanes, and triturated with hexane/EtOAc (10:1) to give the 1-morpholino-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanone (2aaa; 52 mg, 96%) as a white solid

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 767-91-9, its application will become more common.

Reference:
Article; Lee, Doohyun; Kim, Daehun; Lee, Seungyeon; Kim, Taegeum; Kim, Joobin; Kim, Sohee; Liu, Kwang-Hyeon; Lee, Sangkyu; Bae, Jong-Sup; Song, Kyung-Sik; Cho, Chang-Woo; Son, Youn Kyung; Baek, Dong Jae; Lee, Taeho; Molecules; vol. 20; 11; (2015); p. 19984 – 20013;,
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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. 4342-46-5, name is 4-Methoxycyclohexanamine belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Safety of 4-Methoxycyclohexanamine

Water is added to the high-pressure reaction kettle 1200 ml, opening stirring, add concentration is 40% formamide 220 g (2 muM), stirring 10 min after, adding 1 – amino -4 – methoxy cyclohexane 130 g (1 muM), then adding carbon catalyst 7 g, in the reaction kettle access CO, make the kettle pressure reaches 0.2 mpa, heating to 50 C, thermal insulation 20 h, when the reaction solution 1 – amino -4 – methoxy cyclohexane content of less than 2% when the end of the reaction, lowering the temperature to 25 – 30 C, adding diluted hydrochloric acid to the reaction in the fluid drops, adjust the pH to 5 – 6, solids are separated out, to filter out the product, the filter cake washed mixing, cis – 8 – be methoxy – 1, 3 – diaza spiro [4, 5] decan – 2, 4 – dione dry – 155 g, yield 78%

The synthetic route of 4342-46-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Henan Zi Wei Xing Chemical Co., Ltd.; Mao Longfei; Wu Doucan; Li Wei; Lu Zhiguo; Wang Zhenggang; Lu Biao; Jia Shuhong; Yuan Zhiguo; (10 pag.)CN107857722; (2018); A;,
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