Month: July 2021

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

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

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

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

These common heterocyclic compound, 175278-17-8, name is 2-Bromo-4-(trifluoromethoxy)aniline, 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. category: ethers-buliding-blocks

Intermediate 1: 2-propyl-4-(trifluoromethoxy)aniline A solution of 2-bromo-4-(trifluoromethoxy)aniline (256 mg, 1.00 mmol), [(E)-prop-1-enyl]boronic acid (172 mg, 2.00 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (29.0 mg, 0.0400 mmol), and K2CO3(aq) (1 M, 2 equiv) in MeOH (0.5 mL)/toluene (0.5 mL) was stirred at 125 C. for 4 h. The organic layer was separated, concentrated to dryness, and purified by FCC (SiO2) to give (E)-2-(prop-1-en-1-yl)-4-(trifluoromethoxy)aniline. (E)-2-(Prop-1-en-1-yl)-4-(trifluoromethoxy)aniline and Pd/C (10% on carbon, 30 mg) in MeOH (10 mL) was stirred under H2 (1 atm) for 3 h. After filtration on diatomaceous earth such as Celite, the filtrate was collected and concentrated to dryness to give 2-propyl-4-(trifluoromethoxy)aniline. MS (ESI): mass calcd. for C10H12F3NO, 219.1; m/z found, 220.1 [M+H]+.

The synthetic route of 2-Bromo-4-(trifluoromethoxy)aniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Janssen Pharmaceutica NV; Bacani, Genesis M.; Chai, Wenying; Edwards, James P.; Smith, Russell C.; Tichenor, Mark S.; Venable, Jennifer D.; Wei, Jianmei; (64 pag.)US2018/289706; (2018); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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. 588-96-5, name is p-Bromophenetole belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. name: p-Bromophenetole

To a solution of 2R-allyl-3S-hydroxy-succinic acid diisopropylester (4.79 g, 18.5 MMOL), 4-bromo PHENETOLE (3.19 MI, 22.2 mmol, 1.2 eq. ) and NEt3 (6.22 ML, 44.6 MMOL, 2.4 eq. ) in CH3CN (40 ml), was added a sonicated (for 2 min) suspension of P (O-TOL) 3 (0.57 g, 2.22 mmol, 0.1 eq. ) and Pd (OAC) 2 (209 mg, 5%) in CH3CN (5 ML). The reaction mixture was heated to reflux for 2 hrs. CH3CN was removed under vacuum. The crude was extracted with AcOEt (3 X 200 ML), washed with water (50 mi) and with brine (50 ML). A purification by flash chromatography afforded the desired 2R- [3- (4-ethoxy-phenyl)-allyl]-3S- hydroxy-succinic acid diisopropyl ester (5.92 g, 84% yield). 1H-NMR ; delta (CDC13), 7.28 (2H, d, J = 8.8Hz), 6.83 (2H, d, J = 8.8Hz), 6.46 (1H, d, J = 15.7Hz), 6.02-6. 12 (1H, m), 4.98-5. 13 (2H, m), 4.26 (1H, dd, J = 7.1, 3. 0HZ), 4.02 (2H, q, J = 7. 0HZ), 3.23 (1H, d, J = 7. 1 HZ), 2.92-2. 97 (1H, m), 2.68-2. 79 (1H, m), 2.49-2. 62 (1H, m), 1.41 (3H, t, J=7.0 Hz) and 1.19- 1.30 (12H, m). LRMS: +ve ion 400 (M+Na).

The synthetic route of 588-96-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BRITISH BIOTECH PHARMACEUTICALS LTD; LABORATOIRES SERONO S.A.; WO2004/101537; (2004); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Electric Literature of 910251-11-5, 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. 910251-11-5, name is Potassium trifluoro(methoxymethyl)borate belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Methyl (R)-12′-(benzyloxy)-H’-chloro-8′-oxo- ,2′,8′,13b’-tetrahydrospiro[cyclopropane-l,3′- pyrido[2,l-a]pyrrolo[l,2-c]phthalazine]-7′-carboxylate (234 mg, 0.51 mmol) was dissolved in isopropanol (10 mL) with 2 drops of acetic acid. The mixture was stirred at reflux for 2.5 hours, then cooled to room temperature to provide isopropyl (R)-12′-(benzyloxy)-H’-chloro-8′-oxo- ,2′,8′,13b’-tetrahydrospiro[cyclopropane-l,3′-pyrido[2,l-a]pyrrolo[l,2-c]phthalazine]-7′- carboxylate. MS (m/z) 491.3 [M+H]+. The crude ester was combined with (0993) trifluoro(methoxymethyl)-borane, potassium salt (230 mg, 1.52 mmol), Pd RuPhos G4 (52 mg, 0.061 mmol), RuPhos (42 mg, 0.091 mmol), and cesium carbonate (823 mg, 2.53 mmol) in toluene:water (3: 1, 5 mL) under argon in a sealed vial. The mixture was heated at 110 C for 45 minutes with vigorous stirring, then cooled to room temperature, the aqueous layer was removed, and the organics were concentrated in vacuo and purified by flash column (0994) chromatography (hexanes / ethyl acetate / ethanol / triethylamine) to provide isopropyl (R)-12′- (benzyloxy)-i -(methoxymethyl)-8′-oxo- ,2′,8′,13b’-tetrahydrospiro[cyclopropane-l,3′- pyrido[2,l-a]pyrrolo[l,2-c]phthalazine]-7′-carboxylate. MS (m/z) 501.4 [M+H]+.

The synthetic route of Potassium trifluoro(methoxymethyl)borate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GILEAD SCIENCES, INC.; AKTOUDIANAKIS, Evangelos; CANALES, Eda; CURRIE, Kevin S.; KATO, Darryl; LI, Jiayao; LINK, John O.; METOBO, Samuel E.; SAITO, Roland D.; SCHROEDER, Scott D.; SHAPIRO, Nathan; TSE, Winston C.; WU, Qiaoyin; (262 pag.)WO2018/144605; (2018); 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 349-65-5 as follows. Formula: C8H8F3NO

5-(Trifluoromethyl)-2-methoxyaniline was treated with CDI, followed by 4-(1-oxoisoindolin-5-yloxy) aniline according to Method C2d to afford the urea. Entry 26: 4-Hydroxyacetophenone was reacted with 4-fluoronitrobenzene according to Method A13, Step 1 to give 4-(4-acetylphenoxy)nitrobenzene.

According to the analysis of related databases, 349-65-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BAYER CORPORATION; US2002/165394; (2002); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Synthetic Route of 1484-26-0, A common heterocyclic compound, 1484-26-0, name is 3-Benzyloxyaniline, molecular formula is C13H13NO, 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 mixture of triethyl orthoformate (92 ML, 0.55 mol) and 2, 2-DIMETHYL- [1, 3] – dioxane-4,6-dione (75.3 g, 0.522 mol) (Meldrum’s acid) was heated at 55 °C for 90 minutes and then cooled to 45 °C. A solution of 3-benzyloxyaniline (100.2 g, 0.5029 mol) in methanol (200 mL) was slowly added to the reaction over a period 45 minutes while maintaining the reaction temperature below 50 °C. The reaction was then heated at 45 °C for one hour, allowed to cool to room temperature, and stirred overnight. The reaction mixture was cooled to 1 °C, and the product was isolated by filtration and washed with cold ethanol (-400 mL) until the filtrate was colorless. 5-F [ (3- Benzyloxy) phenylimino] METHYL}-2, 2-dimethyl- [1, 3]-dioxane-4, 6-dione (170.65 g) was isolated as a tan, powdery solid. 1H NMR (300MHZ, DMSO-D6) : 8 11. 21 (d, J= 14. 2 Hz, 1H), 8.61 (d, J= 14.2 Hz, 1H), 7.49-7. 30 (m, 7H), 7.12 (dd, J= 8.1, 1.96 Hz, 1H), 6.91 (dd, J= 8.4, 2.1 Hz, 1H), 5.16 (s, 2H), 1. 68 (s, 6H).

The synthetic route of 1484-26-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; 3M INNOVATIVE PROPERTIES COMPANY; WO2005/20999; (2005); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Related Products of 651734-54-2, These common heterocyclic compound, 651734-54-2, name is 2,6-Difluoro-3,5-dimethoxyaniline, 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 mixture of 2,4-dichloro-5-(iodomethyl)pyrimidine (1.50 g, 5.19 mmol), 2,6- difluoro-3,5-dimethoxyaniline (1.08 g, 5.71 mmol) in N,N-diisopropylethylamine (4 mL) was stirred at 80 C for 2 hours. After being cooled to room temperature, the reaction mixture was concentrated under reduced pressure. The residue was purified on silica gel (eluting with 0- 40% EtOAc in DCM) to give 1.70 g of the desired product. LCMS calculated for C13H12CI2F2N3O2 [M+H]+ m/z: 350.0; Found: 350.0.

Statistics shows that 2,6-Difluoro-3,5-dimethoxyaniline is playing an increasingly important role. we look forward to future research findings about 651734-54-2.

Reference:
Patent; INCYTE CORPORATION; LU, Liang; WU, Liangxing; QIAN, Ding-Quan; YAO, Wenqing; (102 pag.)WO2016/134314; (2016); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem