Ethers-buliding-blocks

Electric Literature of 126829-31-0, The chemical industry reduces the impact on the environment during synthesis 126829-31-0, name is 2-Ethynyl-1,3-dimethoxybenzene, I believe this compound will play a more active role in future production and life.

Example 29; [0139] l,3-Bis(2,6-diisopropylphenyl)-4-(2,6-dimethoxyphenyl)-lH-l,2,3-triazolium hexafluorophosphate (lOal). To a stirred suspension of triazene 8a (3.66 g, 10 mmol), 2,6- dimethoxyphenylacetylene 91 (3.24 g, 20 mmol), and anhydrous potassiumhexafluorophosphate (1.84 g, 10 mmol) in dry dichloromethane (50 mL) in the dark at -78C is added tert-butyl hypochlorite (1.66 mL, 15 mmol), upon which the mixture instantly darkens. The mixture is stirred overnight as it is slowly allowed to warm to roomtemperature. The contents are then filtered, and the solid residue is washed withdichloromethane. The filtrate is collected, and volatiles are evaporated under reduced pressure. Diethyl ether is then added, and the mixture is vigorously triturated for ca. Ihour, with occasional scratching of the glass surfaces to ensure efficient mixing. Filtration and washing with copious quantities of diethyl ether afford, after drying under vacuum, triazolium salt lOai as an off-white solid (5.25 g, 78%). Analytical samples were obtained after recrystallization by vapor diffusion of diethyl ether in an acetonitrile solution of lOai. 1H-NMR ((CD3)2SO, 300 MHz): delta = 10.03 (s, 1H), 7.79 (t, J = 7.9 Hz, 1H), 7.64-7.57 (m, 3H), 7.54 (t, J = 7.9 Hz, 1H), 7.42 (d, J = 7.9 Hz, 2H), 6.78 (d, J = 8.5 Hz, 2H), 3.71 (s, 6H), 2.43 (sept, J = 6.8 Hz, 2H), 2.29 (sept, J = 6.8 Hz, 2H), 1.27 (d, J = 6.8 Hz, 6H), 1.17 (d, J = 6.8 Hz, 6H), 1.08 (d, J = 6.8 Hz, 6H), 0.99 (d, J = 6.8 Hz, 6H). 13C-NMR ((CD3)2SO, 75 MHz): delta = 158.4, 145.2, 144.7, 139.9, 136.4, 135.2, 133.3, 132.9, 130.2, 129.2, 125.0, 124.8, 104.7, 98.0, 56.9, 28.8, 28.6, 25.8, 23.8, 23.1, 21.7. HR-MS (ESI): Calcd. for C34H44N302 [M+]: 526.3428, found 526.3433.

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, 2-Ethynyl-1,3-dimethoxybenzene, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; BERTRAND, Guy; GUISADO-BARRIOS, Gregorio; BOUFFARD, Jean; DONNADIEU, Bruno; WO2011/139704; (2011); A2;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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. 62257-15-2, name is 2-Fluoro-5-methoxyaniline, A new synthetic method of this compound is introduced below., HPLC of Formula: C7H8FNO

2-Fluoronicotinic acid methyl ester (0.3 g, 1.934 mmol) and 2-fluoro-5-methoxyaniline(0.278 ml, 2.32 1 mmol) were heated by microwave irradiation at 130 C for 20 mm. SomeDCM was added and the mixture was washed twice with 1120. Organic phase was dried overNa2SO4, filtered and evaporated. Crude product was purified by trituration with diethylether. 0.324 g of the title compound was obtained.?H NMR (400 MHz, CDCJ3) oe ppm 3.82 (s, 3 H) 3.95 (s, 3 H) 6.49 (dt, 1 H) 6.78 (dd, I H) 7.03 (dd, I H) 8.27 (dd, I H) 8.33 (dd, I H) 8.42 (dd, 1 H) 10.42 (hr. s., I H).

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; ORION CORPORATION; ARVELA, Riina; HOLM, Patrik; VESALAINEN, Anniina; WO2015/144976; (2015); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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. 6346-09-4, name is 4,4-Diethoxybutan-1-amine, A new synthetic method of this compound is introduced below., Application In Synthesis of 4,4-Diethoxybutan-1-amine

To 0.95 g 1-isocyanatonaphthalene (5.62 mmol) dissolved in 20 cm3 of dry benzene 0.90 g 4,4-diethoxybutan-1-amine (5.59 mmol) was added. The mixture was stirred at room temperature for 12 h. The precipitate was filtered off,washed with 10 cm3 benzene, and dried in vacuum(0.01 torr, 4 h, r.t.) to give 6 as white solid. Yield 1.63 g(88%); m.p.: 121-122 C (from ethanol); 1H NMR[600 MHz, (CD3)2SO]: d = 1.11 (6H, t, J = 6.86 Hz,CH3), 1.48-1.52 (2H, m, CH2), 1.56-1.60 (2H, m, CH2),3.14-3.17 (2H, m, CH2), 3.42-3.47 (2H, m, CH2),3.55-3.60 (2H, m, CH2), 4.50 (1H, t, J = 5.49 Hz, CH),6.56 (1H, t, J = 5.48 Hz, NH), 7.41 (1H, t, J = 7.96 Hz,CHAr), 7.49-7.55 (3H, m, CHAr), 7.88 (1H, d,J = 8.23 Hz, CHAr), 7.99 (1H, d, J = 7.68 Hz, CHAr),8.08 (1H, d, J = 8.23 Hz, CHAr), 8.44 (1H, s, NH) ppm;13C NMR [150 MHz, (CD3)2SO]: d = 15.8, 25.6, 31.4,39.5, 61.1, 102.6, 116.9, 121.8, 122.4, 125.8, 126.0, 126.2,126.4, 128.8, 134.2, 135.7, 156.1 ppm; MS (MALDITOF):m/z = 353 ([M+Na]+).

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; Smolobochkin, Andrey V.; Gazizov, Almir S.; Voronina, Julia K.; Burilov, Alexander R.; Pudovik, Michail A.; Monatshefte fur Chemie; vol. 149; 3; (2018); p. 535 – 541;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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 437-83-2 as follows. name: 3-Fluoro-2-methoxyaniline

A mixture of 3-fluoro-2-methoxyaniline (1.0 g, 7.1 mmol) and K2CO3 (1.04 g, 7.8 mmol) in DMF (15 mL) was added 1-bromobut-2-yne (981 mg, 7.1 mmol) was stirred at r.t. overnight. The resulting mixture was partitioned between EtOAc and H2O. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to give the crude product which was purified by flash chromatography (silica gel, 0-20% EtOAc in PE) to afford the title compound (552 mg, 40% yield) as a yellow oil. LC-MS (ESI): m/z (M+1) = 193.91.

According to the analysis of related databases, 437-83-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; VIIV HEALTHCARE UK LIMITED; JOHNS, Brian Alvin; VELTHUISEN, Emile Johann; WEATHERHEAD, Jason Gordon; (225 pag.)WO2017/93938; (2017); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem