Category: ethers-buliding-blocks

6346-09-4, These common heterocyclic compound, 6346-09-4, name is 4,4-Diethoxybutan-1-amine, 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.

To a stirred solution of 3-formylbenzoic acid (0.50 g, 3.3 mmol) in DMF (7 mL) was added DIPEA (0.61 mL, 3.5 mmol) and HATU (1.5 g, 4.0 mmol) and the mixture stirred at room temperature for 15 minutes. 4,4-Diethoxybutan-l -amine (0.43 g, 2.68 mmol) was added and the- stirring continued for a further five hours. The reaction mixture was diluted and washed sequentially with aqueous 1M sodium hydroxide, aqueous 2M sodium hydroxide and brine. The organic phase was dried over magnesium sulfate, filtered and the filtrate evaporated at reduced pressure to afford the title compound (0.72 g, 93%). ‘H NMR (400 MHz, DMSO-d6); delta 10.08 (s, 1H), 8.71 (dd, J=5.5, 5.5 Hz, 1H), 8.38 (s, 1H), 8.16 (d, J=7.8 Hz, 1H), 8.06 (d, J=7.7 Hz, 1H), 7.71 (dd, J=7.7, 7.7 Hz, 1H), 4.53 – 4.47 (m, 1H), 3.57 (ddd, J=7.0, 9.5, 14.1 Hz, 2H), 3.43 (ddd, J=7.1, 9.5, 14.1 Hz, 2H), 3.31 – 3.27 (m, 2H), 1.58 – 1.54 (m, 4H), 1.11 (dd, J=7.0, 7.0 Hz, 6H).

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 6346-09-4.

Reference:
Patent; CHIESI FARMACEUTICI S.P.A.; RANCATI, Fabio; RIZZI, Andrea; CARZANIGA, Laura; LINNEY, Ian; (108 pag.)WO2017/93208; (2017); A1;,
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1535-73-5, 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 1535-73-5 as follows.

To a solution of 4-[2-(propargylamino)-2-oxo-acetyl]-1,3,5-trimethyl-pyrrol- 2-carboxylic acid 6 (250 mg, 1.0 mmol), 3-(trifluoromethoxy)aniline (227 mg, 1.3 mmol) and DIPEA (330 muL, 2.0 mmol) in pyridine (10 mL) was added HATU (0.65 g, 1.8 mmol) at room temperature. The mixture was stirred at 65 ¡ãC for 18 h. The reaction mixture was then poured into a saturated solution of ammonium chloride and extracted with ethyl acetate (3 x 50 mL). The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (Hexanes:EtOAc = 6:4 v/v) to give compound 55 as a white powder (34percent, 135 mg, 0.3 mmol). 1H NMR (400 MHz, Acetone-d6) delta 9.57 (s, 1H), 8.18 (s, 1H), 8.02 (s, 1H), 7.81? 7.67 (m, 1H), 7.50 (t, J = 8.2 Hz, 1H), 7.16? 7.06 (m, 1H), 4.17 (dd, J = 5.8, 2.6 Hz, 2H), 3.71 (s, 3H), 2.75 (t, J = 2.5 Hz, 1H), 2.45 (s, 3H), 2.32 (s, 3H). MS (ESI): m/z [M+H]+ calcd for C20H19F3N3O4: 422.4, found: 422.4.

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

Reference:
Patent; EMORY UNIVERSITY; SCHINAZI, Raymond F.; BOUCLE, Sebastien; AMBLARD, Franck; SARI, Ozkan; BASSIT, Leda; (169 pag.)WO2017/156255; (2017); A1;,
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402-52-8, These common heterocyclic compound, 402-52-8, name is 1-Methoxy-4-(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.

Example 249A 1-(2-methoxy-5-(trifluoromethyl)phenyl)ethan-1-one A 250 mL 3-neck round bottom flask equipped with a thermometer and an addition funnel was charged with trifluoromethanesulfonic acid (29.6 mL, 333 mmol) and then treated dropwise (?6 drops/minute) under N2 over 3 hours with a mixture of 4-(trifluoromethyl)anisole (11.74 g, 66.6 mmol) and acetic anhydride (12.57 mL, 133 mmol) keeping the internal temperature at or below 30 C. The resulting mixture was stirred at room temperature for 3 hours and then poured carefully into 150 mL of ice water, adding more ice during the addition to prevent the mixture from warming. The mixture was extracted with methyl tert-butyl ether (twice, 150 mL and 50 mL). The combined methyl tert-butyl ether layers were washed with saturated aqueous NaHCO3 solution 4 times (100 mL, 100 mL, 50 mL and 50 mL). The methyl tert-butyl ether layer was washed with brine, dried (MgSO4), filtered, concentrated, and chromatographed on silica gel, eluting with a gradient of 5% to 10% ethyl acetate in heptane to provide the title compound. 1H NMR (400 MHz, CDCl3) delta ppm 8.00 (dd, J=0.8, 2.5 Hz, 1H), 7.70 (ddd, J=0.8, 2.5, 8.8 Hz, 1H), 7.05 (d, J=8.7 Hz, 1H), 3.97 (s, 3H), 2.62 (s, 3H).

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 402-52-8.

Reference:
Patent; AbbVie S.a.r.l.; Galapagos NV; Altenbach, Robert J.; Bogdan, Andrew; Desroy, Nicolas; Gfesser, Gregory A.; Greszler, Stephen N.; Koenig, John R.; Kym, Philip R.; Liu, Bo; Scanio, Marc J.; Searle, Xenia; Wang, Xueqing; Yeung, Ming C.; Zhao, Gang; (247 pag.)US2018/99932; (2018); A1;,
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1462-37-9,Some common heterocyclic compound, 1462-37-9, name is ((2-Bromoethoxy)methyl)benzene, molecular formula is C9H11BrO, 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.

To a solution of methyl 2-cyanoacetate (0.89 mL, 10.1 mmol) inDMF (20 mL) at rt was added sodium hydride (0.97 g, 24.2 mmol),and the reaction mixture was stirred at rt for 15 min. Tetrabutylammoniumiodide (0.37 g, 1.0 mmol) and ((2-bromoethoxy)methyl)benzene (3.35 mL, 21.19 mmol) were added, and the reactionmixture was stirred at 90 C for 3 h. Water was added and theaqueous layer was extracted with ether (3). The combinedorganic layers were washed with brine, dried over anhydroussodium sulfate, and filtered, and the filtrate was concentrated togive the crude product. The crude product was purified by silicagel chromatography eluting with 0?30percent EtOAc/hexanes to give14 (2.4 g, 65percent yield) as a colorless oil. 1H NMR (500 MHz, CDCl3)d 7.41?7.27 (m, 10H), 4.49 (s, 4H), 3.78?3.69 (m, 5H), 3.45 (s,3H), 2.49?2.40 (m, 2H), 2.06 (dt, J = 14.2, 4.7 Hz, 2H). LC/MS m/z:(M+H)+ calcd for C22H26NO4, 368.19; found 368.3.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1462-37-9, its application will become more common.

Reference:
Article; Wu, Yong-Jin; Guernon, Jason; McClure, Andrea; Luo, Guanglin; Rajamani, Ramkumar; Ng, Alicia; Easton, Amy; Newton, Amy; Bourin, Clotilde; Parker, Dawn; Mosure, Kathleen; Barnaby, Omar; Soars, Matthew G.; Knox, Ronald J.; Matchett, Michele; Pieschl, Rick; Herrington, James; Chen, Ping; Sivarao; Bristow, Linda J.; Meanwell, Nicholas A.; Bronson, Joanne; Olson, Richard; Thompson, Lorin A.; Dzierba, Carolyn; Bioorganic and Medicinal Chemistry; vol. 25; 20; (2017); p. 5490 – 5505;,
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The chemical industry reduces the impact on the environment during synthesis 2252-44-0, name is 3-(Trifluoromethoxy)bromobenzene, I believe this compound will play a more active role in future production and life. 2252-44-0

EXAMPLE 92 (RR,SS)-3-(2-methoxyphenyl)-2-methyl-3-(1-naphthyl)-2-({4-[3-(trifluoromethoxy)phenyl]piperazin-1-yl}carbonyl)propanenitrile (RR,SS)-3-(2-methoxyphenyl)-2-methyl-3-(1-naphthyl)-2-(piperazin-1-ylcarbonyl)propanenitrile (377 mg, 0.913 mmol), meta-trifluoromethoxy bromobenzene (200 mg, 0.830 mmol), sodium tert-butoxide (111 mg, 1.16 mmol), tris(dibenzylideneacetone) dipalladium (0) (22.8 mg, 0.025 mmol), racemic BINAP (31 mg, 0.05 mmol), and toluene (3 mL) were combined in a Carius tube, vacuum degassed, placed under an argon atmosphere, sealed and heated to 80 C. overnight. The reaction was cooled, taken up in diethyl ether, filtered, washed with water, saturated aqueous sodium bicarbonate, brine, dried over MgSO4, filtered, evaporated, and purified on slica gel (10% hexanes/CH2Cl2) to yield 255 mg of the title compound as a white powder. 1H NMR 500 MHz (DMSO-D6): delta 7.97 (d, 1H, J=7.18 Hz), 7.88 (m, 1H), 7.84 (m, 1H), 7.78 (d, 1H, J=8.25 Hz), 7.52 (t, 1H, J=7.48 Hz), 7.41 (m, 2H), 7.30 (t, 1H, J=8.25 Hz), 7.23 (td, 1H, J=7.79 Hz, 1.68 Hz), 7.12 (m, 2H), 6.91 (dd, 1H, J=8.40 Hz, 1.68 Hz), 6.79 (m, 2H), 6.72 (d, 1H, J=8.09 Hz), 6.01 (s, 1H), 4.01 (s, 3H), 3.68 (bs, 4H0, 3.16 (bs, 4H) 1.63 (s, 3H) MS (ESI) m/z 574 ([M+H]+); Anal. calcd for C33H30F3N3O3. 0.35 C6H14: C, 69.82; H, 5.83; N, 6.96. Found: C, 69.81 H, 5.91; N, 6.74.

The chemical industry reduces the impact on the environment during synthesis 2252-44-0. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Wyeth; US2005/256132; (2005); A1;,
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22236-10-8, A common heterocyclic compound, 22236-10-8, name is 4-(Difluoromethoxy)aniline, molecular formula is C7H7F2NO, 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: N-formylation of amines by CO2 and DMAB in the presence of UiO-66 as a catalyst was carried out in autoclave. The synthesis of formamides is as follows, Amines (5.0 mmol), UiO-66 (10 mg), DMAB (1.5 equiv.), DMF (7 mL) were added in the reactor at room temperature, reactor was closed, flushed two to three times by CO2 and 1 MPa CO2 pressure was introduced into reactor, then the reactor was heated to required temperature with continuous stirring. After the reaction was complete, the reactor was cooled, and the CO2 pressure was carefully discharged from the autoclave. The UiO-66 MOF was separated by centrifugation. The resultant mixture was concentrated by rotary evaporator and subjected to the column chromatography with ethyl acetate-petroleum ether used as an eluent to obtain the product. All the products are confirmed by GCMS.

The synthetic route of 22236-10-8 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Phatake, Vishal V.; Mishra, Ashish A.; Bhanage, Bhalchandra M.; Inorganica Chimica Acta; vol. 501; (2020);,
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The chemical industry reduces the impact on the environment during synthesis 1535-75-7, name is 2-(Trifluoromethoxy)aniline, I believe this compound will play a more active role in future production and life. 1535-75-7

2-Trifluoromethoxyaniline (0.8Og, 5.0mmol) and sodium hydride (60% dispersion in mineral oil, 1.7eq) were stirred in dry DMF at room temperature for 2 hours, and 5-bromo- 2-chloropyridine (1.0Og, 5.0mmol) was added and the mixture stirred at room temperature overnight. Iced water was added slowly to the mixture, and the mixture was extracted with DCM (3x). The DCM was washed with 2M HCl solution (2x), dried (MgSO4), and concentrated. The residue was purified by column chromatography eluting using a gradient (EtOAc/hexanes 1 :9 v/v).

The chemical industry reduces the impact on the environment during synthesis 1535-75-7. I believe this compound will play a more active role in future production and life.

Reference:
Patent; BioMarin IGA, Ltd.; WREN, Stephen Paul; WYNNE, Graham Michael; LECCI, Cristina; WILSON, Francis Xavier; DAVIS, Paul James; WO2010/57833; (2010); A1;,
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2930-05-4, 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. 2930-05-4, name is 2-((Benzyloxy)methyl)oxirane belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

General procedure: In a typical procedure, an admixture comprising of a solid cata-lyst (20 mg), an aryloxy epoxide (1 mmol) and an amine (1 mmol)were taken in a 5 mL screw capped vial and stirred vigorously fora given time period (monitored by TLC) under solvent free con-dition. At the end of the reaction, products amino alcohols wereobtained as viscous liquids or solids. Therefore, the reaction mix-ture was repeatedly washed with methanol (3 mL) and centrifuged.Methanol from the combined organic layer was evaporated underreduced pressure to get crude amino alcohol. A small sample of thecrude product was subjected to HPLC to find out regioselectivity,while rest of the reaction mixture was subjected to flash columnchromatography (hexane/ethyl acetate, 90:10) to get the majorregioisomer in pure form. The purified product was characterizedby1H and13C NMR, FTIR, Microanalysis and characterization datafor all the ring opening products are given in supporting informa-tion. The residue obtained from centrifugation was dried in air (1 h)and then in oven at 100C for 3 h to get back the catalyst (>97%recovery) for further use.

The synthetic route of 2930-05-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Shah, Arpan K.; Prathap, K. Jeya; Kumar, Manish; Abdi, Sayed H.R.; Kureshy, Rukhsana I.; Khan, Noor-ul H.; Bajaj, Hari C.; Applied Catalysis A: General; vol. 469; (2014); p. 442 – 450;,
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A common compound: 702-24-9, name is 4-Methoxy-N-methylbenzylamine, belongs to ethers-buliding-blocks compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below. 702-24-9

A mixture of ethyl 6-bromopyrazolo[1,5-a]pyrimidine-3-carboxylate (1.5 g, 5.55 mmol), N-(4- methoxybenzyl)-N-methylamine (1.67 g, 11.04 mmol) and N,N-diisopropylethylamine (2.75 ml, 16.63 mmol) in ethanol (25ml) was stirred at 85 ¡ãC for 96h. The mixture was concentracted to dryness and the residue was purified by column chromatography (eluent 50percent ethyl acetate: petroleum ether) to afford ethyl 6-[(4-methoxyphenyl)methyl-methyl-amino]pyrazolo[1,5- a]pyrimidine-3-carboxylate (1120 mg, 57.5percent yield) as a yellow solid. (ESI): m/z = 341.2 [M+1]+.

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, 702-24-9, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; BRYAN, Marian, C.; GOBBI, Alberto; KIEFER, James, Richard, Jr.; KOLESNIKOV, Aleksandr; OLIVERO, Alan, G.; DROBNICK, Joy; LIANG, Jun; RAJAPAKSA, Naomi; (846 pag.)WO2017/108723; (2017); A2;,
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Some common heterocyclic compound, 54149-17-6, name is 1-Bromo-2-(2-methoxyethoxy)ethane, molecular formula is C5H11BrO2, 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. 54149-17-6

Example 20 Synthesis and Utility of 2,7-dibromo-9,9-bis(3,6-dioxaheptyl)-fluorene Benzyltriethylammonium chloride (3.19 g, 14 mmole, 0.077 eq) and 2,7-dibromofluorene (59 g, 182 mmole, 1 equiv.) were suspended in 178 mL DMSO. 50% aqeous NaOH 80 mL was added. 1-Bromo-2-(2-methoxyethoxy)ethane (80 g, 437 mmole, 2.4 equiv.) was then added in small portions. The reaction was stirred at room temperature for 2 hours before it was stopped and the aqueous layer was extracted with ether. The combined ether layers were washed with water five times and dried over Na2SO4. The organic layer was filtered, evaporated to dryness and the residual was flash chromatographed on a silica-gel column to give the pure compound (73 g), in a yield of 86%. This compound can be used for example to modify the solubility parameter of the compound of Example 16. To do this 2,7-dibromo-9,9-bis(3,6-dioxaheptyl)-fluorene is used in place of 2,7-dibromo-9,9-dioctyl fluorene in Example 16.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 54149-17-6, its application will become more common.

Reference:
Patent; 3M Innovative Properties Company; US7271406; (2007); B2;,
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