Author: Jessica.F

Reference of 103-50-4,Some common heterocyclic compound, 103-50-4, name is Benzyl ether, molecular formula is C14H14O, 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.

At 100 and at a pressure of 1.5MPa, ozone (30% by volume, the remainder being an equal volume of helium and oxygen) as the oxidant, the benzyl ether, the ozone and the solvent is acetonitrile according 1:2:60 The molar ratio of reaction.Results two hours the reaction is as follows: benzyl ether conversion was 43%; 51% selectivity to benzoic acid. This example illustrates the process and results in a reaction solvent is acetone time.The reaction conditions according to Example 11 is reacted, except that the use of acetone instead of acetonitrile as solvent.Results two hours the reaction is as follows: benzyl ether conversion was 58%; 56% selectivity to benzoic acid. This example illustrates the presence of a catalyst in the reaction process and results.In HTS catalyst, the molar ratio of the catalyst with the benzyl ether 1:10, ozone LHSV of 1000h-1, the other reaction conditions as in Example 12.Results two hours the reaction is as follows: benzyl ether conversions of 73%; 64% selectivity to benzoic acid.

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

Reference:
Patent; China Petroleum & Chemical Corporation; SINOPEC Research Institute of Petroleum Processing (RIPP); Zhu, bin; Shi, Chunfeng; Lin, Min; (8 pag.)CN103288631; (2016); B;,
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Electric Literature of 82830-49-7, 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. 82830-49-7, name is 2-Fluoro-1,4-dimethoxybenzene belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

A 10 mL oven-dried Schlenk tube was charged with magnesium (57.6 mg, 2.4 mmol) and anhydrous THF (1.5 mL), 5 drops of diisobutylaluminium hydride (DIBAL) was added and stirred for 5 min to activate magnesium. 2-bromo-1,3,5-triisopropylbenzene (566 mg, 2 mmol) was added potion-by-potion with vigorous stirring. The tube was capped with a rubber septum and was heated to 70 C. for 2 h (A). In another 10 mL oven-dried Schlenk tube was charged with 2-fluoro-1,4-dimethoxybenzene (156 mg, 1 mmol) and anhydrous THF (3.5 mL). The tube was cooled to -78 C. and 1.6 M n-BuLi solution in hexane (0.64 mL, 1 mmol) was added dropwise over 10 min under vigorous stirring. The mixture was stirred at -78 C. for 40 min (B). A was transferred into to B by syringe over 15 min at -78 C. An additional 1 mL of THF was used to rinse the reaction and was also transferred to B. The combined reaction mixture was stirred at -78 C. for another 1 h and then slowly warmed to room temperature and vigorously stirred for overnight. At this time, the mixture was cooled to 0 C. using ice bath, and iodine (762 mg, 3 mmol) in 4 mL anhydrous THF was added drop-wise over 5 min, then the reaction mixture was stirred for 30 min, and then warmed to stir at room temperature for 2 h. Then, the mixture was quenched with saturated Na2S2O3 (aq.) solution until the red color of bromine disappeared. The aqueous phase was extracted with Et2O (10 mL×3) and the combined organic phases were dried over anhydrous MgSO4. After concentration, the crude product was purified by silica gel chromatography (EtOAc/petroleum ether=1/20) followed by crystallization in methanol to get a white solid (162 mg, 30%), labeled as 25MeOTIP-I. 1H NMR (600 MHz, Chloroform-d) delta 7.39-7.29 (m, 4H), 7.28-7.24 (m, 1H), 7.21 (s, 1H), 6.90 (d, J=8.9 Hz, 1H), 6.82 (d, J=8.9 Hz, 1H), 3.91 (s, 3H), 3.71 (s, 3H), 2.66 (p, J=7.2 Hz, 1H), 2.55-2.45 (m, 1H), 2.34 (p, J=6.8 Hz, 1H), 1.23 (d, J=6.9 Hz, 3H), 1.11 (dd, J=12.6, 6.9 Hz, 6H), 1.04 (d, J=6.8 Hz, 3H), 0.81 (d, J=7.2 Hz, 3H), 0.72 (d, J=7.2 Hz, 3H) ppm. 13C NMR (151 MHz, Chloroform-d) delta 152.42 (d, J=24.3 Hz), 147.34, 145.33, 141.78, 137.81, 137.38, 137.03, 131.88, 131.03, 126.95, 126.24, 119.68, 109.92, 109.16, 56.81, 55.32, 32.61, 30.91, 29.66, 24.68 (d, J=2.3 Hz), 24.06, 23.75, 22.91 (d, J=21.4 Hz) ppm.

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-Fluoro-1,4-dimethoxybenzene, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Agency for Science, Technology and Research; Johannes, Charles W.; Robins, Edward G.; Jong, Howard; Lim, Yee Hwee; Chia, Saei Weng; Yang, Yong; Podichetty, Anil; (84 pag.)US2016/207034; (2016); A1;,
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Synthetic Route of 1535-73-5, 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. 1535-73-5, name is 3-Trifluoromethoxyaniline belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

A solution of NBS (20.1 g, 111.9 mmol) in DMF (40 mL) was added drop wise to a solution of 3-trifluoromethylaniline (20.0 g, 112.9 mmol) in DMF (80 mL) at room temperature over 40 minutes. The reaction mixture was stirred overnight.After 12 h, the reaction mixture was poured into water and extracted with EtOAc and the organic layer was dried over anhydrous Na2SO4. Concentration in vacuo gave 26 g of Preparation 67A. [00514] MS (ES): m/z = 256.2 [M+lf .

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

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; WO2009/3077; (2008); A1;,
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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. 588-96-5, name is p-Bromophenetole, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 588-96-5

Ethyl 1-(4-ethoxyphenyl)-1H-pyrazole-3-carboxylate (2) A 10 mL Schlenk tube was dried under vacuum, filled with nitrogen and consecutively charged with 19.4 mg (0.102 mmol, 0.2 eq) Cul, 332.3 mg (1.020 mmol, 2.0 eq) Cs2CO3, 100.0 mg (0.714 mmol, 1.4 eq) ethyl 1H-pyrazole-3-carboxylate (6), 102.4 mg (73.0 muL, 0.510 mmol, 1.0 eq) p-bromophenetol and 1 mL dry ACN. The light brown suspension was degassed by vaccum/N2 cycles and stirred first at 82 C. for 7 h and than after adding 0.5 mL dry DMF (solubility issue) at 120 C. for further 65 h. The GC-MS analysis showed full conversion. ACN and DMF were removed under high pressure and the brown residue was suspended in 10 mL EtOAc. After filtration of the brown suspension through a pad of silica and flushing with 150 mL EtOAc the colorless filtrate was concentrated under reduced pressure leading to 52.1 mg (39%) crude product as a green-brown oil. Final purification by column chromatography (CH/EtOAc 3:1, size: 15.5*2.0 cm, 20 g silica gel) yielded the pure title compound. yield: 10.2 mg (8%); orange solid; M.p.: 88-90 C.; Rf (CH/EtOAc 3:1): 0.40; 1H-NMR (300 MHz, DMSO-d6): delta (ppm)=8.51 (d, 4J=2.4 Hz, 1H, Ar-H), 7.78 (d, 3J=9.0 Hz, 2H, Ar-H), 7.07 (d, 3J=9.0 Hz, 2H, Ar-H), 6.97 (d, 4J=2.4 Hz, 1H, Ar-H), 4.31 (q, 3J=6.9 Hz, 2H, CH2), 4.08 (q, 3J=7.2 Hz, 2H, CH2), 1.37-1.29 (m, 6H, 2 CH3); 13C-NMR (75.5 MHz, DMSO-d6): delta (ppm)=161.4 (C=O), 157.6 (Cq), 143.6 (Cq), 132.5 (Cq), 129.5 (CHAr), 120.7 (2CHAr), 115.0 (2CHAr), 119.8 (CHAr), 63.4 (CH2), 60.3 (CH2), 14.5 (CH3), 14.1 (CH3); GC-MS (NM-50_S2): tR=7.722 min (m/z=260.1, 98.0% M+, BP).

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 588-96-5.

Reference:
Patent; Technische Universitaet Graz; Karl-Franzens-Universitaet Graz; Schweiger, Martina; Romauch, Matthias; Zimmermann, Robert; Mayer, Nicole; Breinbauer, Rolf; US9206115; (2015); B2;,
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Related Products of 93919-56-3, These common heterocyclic compound, 93919-56-3, name is (4-(Trifluoromethoxy)phenyl)methanamine, 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.

General procedure: To a solutionof the corresponding aldehyde (1.2 eq.; unless stated otherwise) in DMF (2 inL per 0.3 mmol of aldehyde; unless stated otherwise) was added the corresponding amine (2.5 eq.; unless stated otherwise) and the resulting solution was stirred at 25 C to form the corresponding inline. Then, the corresponding isocyano(tosyl)methyl)arene reagent (1 eq.; unless stated otherwise) and K2CO3 (1.5 eq.; unless stated otherwise*) were added and the reaction mixture was stirred at 25 C (unless stated otherwise). The reaction was stopped after the time indicated for each particular reaction. The reaction progress was monitored by TLC. (0083) A saturated aqueous solution of NH4CI (10 mL per 1 mmol of aldehyde) was added to the reaction mixture, which was then extracted with EtOAc (2 x 30 mL per 1 mmol of aldehyde). The combined organic extracts were washed with H2O (2 x 25 mL per 1 mmol of aldehyde), dried over MgSCC, filtered, and the solvent was evaporated in vacuo to provide the crude product. The residue obtained after the workup was purified using column chromatography or preparative TLC (unless stated otherwise). (0084) * note: in cases when the amine was used as HC1 salt, 4 eq. of K2CO3 were used

Statistics shows that (4-(Trifluoromethoxy)phenyl)methanamine is playing an increasingly important role. we look forward to future research findings about 93919-56-3.

Reference:
Patent; MASARYKOVA UNIVERZITA; BRYJA, Vitezslav; JANOVSKA, Pavlina; GREGOROVA, Michaela; NEMEC, Vaclav; KHIRSARIYA, Prashant; PARUCH, Kamil; (171 pag.)WO2019/185631; (2019); A1;,
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Reference of 5961-59-1, A common heterocyclic compound, 5961-59-1, name is 4-Methoxy-N-methylaniline, molecular formula is C8H11NO, 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.

A solution of 62 (tert-butoxycarbonyl)-l-phenylalanine (1, 8.75mmol, 2.3g) in 15mL 63 dichloromethane was added PyBop (10.9mmol, 5.7g) at 0C, and the mixture stirred for 0.5h. Subsequently, 64 DIEA (21.87mmol, 3.61mL) and 25 4-methoxy-N-methylaniline (7.29mmol, 1.0g) were added to the mixture and then stirred at room temperature for another 8-9h (monitored by TLC). The resulting mixture was evaporated under reduced pressure and the residue was initially washed by 1N HCl and extracted with ethyl acetate (3×20mL). Then, the combined organic layer was washed with saturated sodium bicarbonate (3×50mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford corresponding crude intermediate 65 2 as yellow oil with a yield of 94%. 1H NMR (400MHz, DMSO-d6) delta 7.21 (d, J=8.4Hz, 3H), 7.15 (d, J=7.1Hz, 2H), 7.02 (d, J=8.4Hz, 2H), 6.85-6.75 (m, 2H), 4.15 (q, J=5.4Hz, 1H), 3.80 (s, 3H), 3.12 (s, 3H), 2.81-2.54 (m, 2H), 1.30 (s, 9H). 13C NMR (100MHz, DMSO) delta 172.21, 158.98, 155.74, 138.53, 136.13, 129.28, 128.47, 126.70, 115.21, 78.33, 55.94, 53.53, 37.86, 37.10, 28.65. ESI-MS: m/z 385.4 (M+1)+, C22H28N2O4 (384.2)

The synthetic route of 5961-59-1 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Wu, Gaochan; Zalloum, Waleed A.; Meuser, Megan E.; Jing, Lanlan; Kang, Dongwei; Chen, Chin-Ho; Tian, Ye; Zhang, Fangfang; Cocklin, Simon; Lee, Kuo-Hsiung; Liu, Xinyong; Zhan, Peng; European Journal of Medicinal Chemistry; vol. 158; (2018); p. 478 – 492;,
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Reference of 934240-59-2, 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 934240-59-2 as follows.

To a mixture of magnesium turnings (12.79g. 533mol), a trace of iodine and 1 ,2-dibromoethane in THF (86.ml)at 70-750C, a solution of (4-bromophenyl (2- fluorophenyl)methyl ether) (100g, 355.6mmol) in THF (216.25ml) was added over about 2 hours. The mixture was heated for a further 2 hours at 70-75C then cooled to room temperature to give a solution of the Grignard reagent. A solution of 1-(1 ,1-dimethylethyl) 2-methyl (2S)-5-oxo-1 ,2-pyrrolidinedicarboxylate (43.25g, 177.8mmol) in THF (216.25ml) was cooled to -600C and the solution of the Grignard reagent was added over 1 hour, then the mixture was stirred for 3 hours at -60C. lsopropanol (43.25ml) was added dropwise, followed by saturated aqueous ammonium chloride (86.5ml) and brine (43.25ml), then the mixture warmed to room temperature. Water (173ml) and 50% acetic acid (50ml) to pH 6- 7, followed by ethyl acetate (129.7ml). The layers were separated and the aqueous extracted with ethyl acetate (2 x 129.7ml). The combined organic layers were washed with brine then concentrated under vacuum. The residue was stirred with hexane (216.2ml), then the solid was filtered and washed with hexane. To the resulting solid, isopropanol (432.5ml) was added and the mixture stirred at 45C for 15 minutes, then cooled to 5- 100C and stirred for 2 hours. The solid was filtered, washed with isopropanol and dried to give the title compound as a solid.1 H NMR (300 MHz, CHCI3-d): delta(ppm): 1.42 (s, 9H); 2.04 (m, 1 H); 2.28 (m, 1 H); 3.03 (m, 2H); 3.74 (s, 3H); 4.37 (m, 1 H); 5.19 (b, 1 H); 5.20 (s, 2H); 7.02 (d, 2H); 7.1 1 (t, 1 H); 7.17 (t, 1 H); 7.33 (m, 1 H); 7.48 (t, 1 H); 7.94 (d, 2H).

According to the analysis of related databases, 934240-59-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; GLAXO GROUP LIMITED; WO2008/90114; (2008); A1;,
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Adding a certain compound to certain chemical reactions, such as: 38336-04-8, name is 2-(Benzyloxy)-1-ethanamine, 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 38336-04-8, SDS of cas: 38336-04-8

In a sealable vial, a solution of compound 173 (0.71 g, 2.81 mmol) and 2-(benzyloxy)-l-ethaneamine (0.85 g, 5.62 mmol) in benzene (20 mL) was flushed with N2. The vial was sealed and heated at 80 C for 4 h. After cooled to room temperature, the reaction mixture was partitioned between sat. aq. KH2PQ4 (50 mL) and EtOAc (50 mL). The organic extract was washed with brine (50 mL), dried with MgSOr, filtered, and concentrated. The residue was purified by column chromatography (silica gel, eluting with 25% EtOAc in hexanes) to give compound 269e (0.91 g, 84% yield) as a light yellow oil. m/z = 386 (M+l).

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

Reference:
Patent; REATA PHARMACEUTICALS, INC.; JIANG, Xin; VISNICK, Melean; BENDER, Christopher, F.; BOLTON, Gary; CAPRATHE, Bradley; LEE, Chitase; KORNBERG, Brian; O’BRIEN, Patrick; HOTEMA, Martha, R.; (420 pag.)WO2019/241796; (2019); A1;,
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Electric Literature of 446-59-3, 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. 446-59-3, name is 2-Bromo-1-fluoro-3-methoxybenzene, This compound has unique chemical properties. The synthetic route is as follows.

Synthesis of 3-Bromo-2-fluoro-4-methoxy-benzaldehyde In a 3-neck 250 mL round bottomed flask equipped with nitrogen lines and a stir bar was placed 2-bromo-1-fluoro-3-methoxy-benzene (2.0 g, 9.75 mmol) and dichloromethane (48 mL). The solution was cooled in an ice water bath for 15 minutes and then titanium tetrachloride (5.02 mL, 45.8 mmol) and dichloromethyl methyl ether (1.32 mL, 14.6 mmol) were added and the reaction mixture was allowed to warm to room temperature and react for 2 hours. The reaction mixture was slowly added to ice water (250 mL) and extracted with dichloromethane (2*100 mL). The organic portions were combined, washed with a saturated sodium bicarbonate solution (75 mL), water (75 mL) and brine (75 mL), dried (MgSO4) and concentrated. The crude material was triturated with hexanes (15 mL) to produce 1.67 g of Int-4 as an off-white solid in 74% yield. MS (ESI+): 233.2 (M+) Int-17Synthesis of 3-Bromo-2-fluoro-4-methoxy-benzaldehyde using titanium(IV)chlorideA solution of 2-bromo-3-fluoroanisol (5.00 g, 24.3 mmol) in dichloromethane (120 mL) was cooled to 0 C. in a salt-ice bath and purged with nitrogen. The reaction was allowed to stir 15 min under nitrogen. To the reaction was added titanium(IV)chloride (23.1 g, 122 mmol), followed by a,a-dichloromethyl-methylether (4.21 g, 36.6 mmol) at 0 C. under nitrogen. The reaction was allowed to warm to room temperature and stirred for 22 h. The red solution was poured into ice water (600 mL), and extracted into dichloromethane (3×200 mL). The organic extracts were combined, washed with saturated aqueous sodium bicarbonate (2×400 mL), water (2×400 mL), and brine (400 mL), dried over sodium sulfate, filtered, and the solvent removed under vacuum to give wet product. The product was dried in a vacuum oven at 80 C. overnight to give Int-17 (5.75 g, quantitative yield).1H NMR (400 MHz CDCl3) delta 10.22 (s, 1H), 7.86 (dd, J=8.8 Hz, 7.6 Hz, 1H), 6.82 (d, J=8.4 Hz, 1H), 4.01 (s, 3H). Synthesis of 3-bromo-2-fluoro-4-methoxy-benzaldehyde (I-30). In a 3-necked 250 mL round-bottomed flask equipped with nitrogen lines and a stir bar was placed 2-bromo-1-fluoro-3-methoxy-benzene (I-29, 2.0 g, 9.75 mmol) and dichloromethane (48 mL). The solution was cooled in an ice water bath for 15 minutes and then titanium tetrachloride (5.02 mL, 45.8 mmol) and dichloromethyl methyl ether (1.32 mL, 14.6 mmol) were added and the reaction mixture was allowed to warm to room temperature and react for 2 hours. The reaction mixture was slowly added to ice water (250 mL) and extracted with dichloromethane (2×100 mL). The organic portions were combined, washed with a saturated sodium bicarbonate solution (75 mL), water (75 mL) and brine (75 mL), dried (MgSO4) and concentrated. The crude material was triturated with hexanes (15 mL) to produce 1.67 g of 3-bromo-2-fluoro-4-methoxy-benzaldehyde (I-30) as an off-white solid in 74% yield. MS (ESI+): 233.2 (M+).

The chemical industry reduces the impact on the environment during synthesis 2-Bromo-1-fluoro-3-methoxybenzene. I believe this compound will play a more active role in future production and life.

Reference:
Patent; DECODE GENETICS EHF; US2009/136473; (2009); A1;,
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38336-04-8, name is 2-(Benzyloxy)-1-ethanamine, belongs to ethers-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. SDS of cas: 38336-04-8

To a mixture of Boc-Ala-OSu (6.08 g, 21.2 mmol) in DCM (40 mL) was added dropwise a solution of 2-(benzyloxy)-1-ethanamine (3.38 g, 22.3 mmol) in DCM (10 mL) at 0 oC. The mixture was allowed to slowly warm to room temperature overnight. After 23 h, the reaction mixture was quenched with saturated NaHCO3, extracted with DCM (3x), dried over Na2SO4. After the solvent was evaporated under reduced pressure, the residue was purified by flash chromatography on silica gel (120 g column) eluted with 0 to 50% ethyl acetate/hexanes to afford tert-butyl (S)-(1-((2- (benzyloxy)ethyl)amino)-1-oxopropan-2-yl)carbamate (6.87 g). ESI-MS m/z 345.2 (M+Na)+, 267.2 (M+H-56)+.

The synthetic route of 38336-04-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; VENATORX PHARMACEUTICALS, INC.; BURNS, Christopher J.; DAIGLE, Denis; CHU, Guo-Hua; HAMRICK, Jodie; BOYD, Steven A.; ZULLI, Allison L.; MESAROS, Eugen F.; CONDON, Stephen M.; TROUT, Robert E. Lee; MYERS, Cullen L.; XU, Zhenrong; (327 pag.)WO2019/226931; (2019); A1;,
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