Author: Jessica.F

Reference of 7664-66-6, A common heterocyclic compound, 7664-66-6, name is 4-Isopropoxyaniline, molecular formula is C9H13NO, 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 solution of 1,1′-carbonyldiimidazole (23.3 mg, 0.144 mmol) in DCM (1 mL) was added 4-isopropoxyaniline (21.7 mg, 0.144 mmol). After stirring at 0 C. for 2 h, 1-thieno[2,3-d]pyrimidin-4-yl-piperidin-4-ol (33.7 mg, 0.143 mmol), as prepared in Example 1a, was added and stirred at RT. After 2 h, DMAP (17.6 mg, 0.144 mmol) was added and stirred at 85 C. overnight. The reaction was then cooled to RT, partitioned between DCM (10 mL) and H2O (10 mL). The organic phase was dried over Na2SO4 and concentrated in vacuo. Purification by prep tlc (1:1 Hexane/EtOAc) afforded the title compound as a light green solid (8.4 mg, 14%). 1H NMR (300 MHz, CDCl3) delta 8.7 (br s, 1H), 7.44 (br m, 1H), 7.29 (m, 3H), 6.85 (m, 2H), 6.56 (br s, 1H), 5.09 (m, 1H), 4.48 (heptet, 1H), 4.17 (m, 2H), 3.75 (m, 2H), 2.11 (m, 2H), 1.87 (m, 2H), 1.31 (d, 6H). LC/MS (ESI): calcd mass 412.2, found 413.2 [M+1]+.

The synthetic route of 7664-66-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Baumann, Christian Andrew; Gaul, Michael David; US2006/281769; (2006); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

These common heterocyclic compound, 1758-46-9, name is 2-Phenoxyethylamine, 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. Safety of 2-Phenoxyethylamine

[0332] A mixture of 2-phenoxyethan-1-amine (10 mmol, 1.0 equiv), 1H-pyrazole-1-carboxamidine hydrochloride (15 mmol, 1.5 equiv, 1 M) and DIPEA (1.5 equiv) in 1,4-dioxane/H20 (2:1) was refluxed for 8 hours, cooled down to r.t. and evaporated to dryness. Anorange oily residue was treated with water and resulting solution was saturated with solid K2C03 to induce the precipitation of free guanidine. Formed precipitate was filtered off, washed withcold water and dried on a rotary evaporator to afford a title compound. Yield: 0.878 g (49percent).

The synthetic route of 2-Phenoxyethylamine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; EVERON BIOSCIENCES, INC.; GUDKOV, Andrei; POLINSKY, Alexander; BALAN, Vitaly; CHERNOVA, Olga; HALL, Brandon, M.; KOMAROB, Pavel, G.; KAZYULKIN, Denis, N.; (236 pag.)WO2017/189553; (2017); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Reference of 5905-69-1,Some common heterocyclic compound, 5905-69-1, name is 1-Bromo-4-(difluoromethoxy)benzene, molecular formula is C7H5BrF2O, 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.

Step 3. Synthesis of ethyl 5-(4-(difluoromethoxy)phenyl)isoxazole-3- carboxylate [1.2.11c] 1.2.11c A vial was charged with 1.2.11 b (0.76 g, 1.77 mmol, 1.0 equiv) and 1-bromo-4- uoromethoxy) benzene (0.5 g, 2.13 mmol, 1.2 equiv) were dissolved in 1 ,4-dioxane (10 ml_). Pd(PPh3)2CI2 (0.062 g, 0.085 mmol, 0.05 equiv) was added and the reaction mixture was stirred at 130 C for 2 hours. The reaction mixture was quenched with water and extracted with EtOAc. The organic layer was washed with brine, dried over sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (0-10 % EtOAc in Hexane) to afford product 1.2.11c (0.6 g, 94 % yield). LCMS (m/z): 284.2 [M+H]. 1H NMR (400 MHz, CDCI3) delta 7.89 – 7.81 (m, 2H), 7.28 – 7.24 (m, 2H), 6.93 (s, 1 H), 6.4 – 6.9 (3s, 1 H), 4.19 (q, J = 7.1 Hz, 2H), 1.31 – 1.29 (t, 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-4-(difluoromethoxy)benzene, its application will become more common.

Reference:
Patent; NOVARTIS AG; FU, Jiping; KARUR, Subramanian; MADERA, Ann Marie; PECCHI, Sabina; SWEENEY, Zachary Kevin; TJANDRA, Meiliana; YIFRU, Aregahegn; WO2014/160649; (2014); 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. 54149-17-6, name is 1-Bromo-2-(2-methoxyethoxy)ethane, A new synthetic method of this compound is introduced below., Safety of 1-Bromo-2-(2-methoxyethoxy)ethane

Example 1: Synthesis of ironflID /wgyo-tetrakis(N.N-di-(2-(2-methoxyethoxy)ethv?- imidazol-2-vnporphyrin (6) ;(“FeTDPImP”)FeTDPImp (FW: 1626.2 g/mol) was synthesized from a starting imdizaole compound using the following synthetic scheme. The synthetic scheme is shown, along with structures of intermediate products, in FIGS. 2A and 2B.1. Synthesis of N-( 2-(2-methoxyethoxy)ethvI>imidazole (2)Imidazole Ig (0.015 mol) was dissolved in dry DMF 50 mL under argon atmosphere. After a NaH mineral oil dispersion (60%) 0.68g (0.017mol) was added, the mixture was heated at 80 0C for 70 min. After cooling to room temperature, l-Bromo-2- (2-methoxyethoxy)-ethane (1), 2.75 g (0.015 mol), was added, then stirred overnight. The reaction was poured into water, extracted by CHCb, washed by water, dried over Na?SCU, then dried (Rotavap) until an oily residue remained. The crude product was purified with silica gel flash column chromatography with an eluant of CHCh : CH3<_)H=20: 1. 1.69 g(70% yield) of the product (2) was obtained as a colorless oil. As an alternative to column chromatography, product (2) is purified by vacuum distillation

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; TRUSTEES OF PRINCETON; WO2008/45358; (2008); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Synthetic Route of 31804-36-1, These common heterocyclic compound, 31804-36-1, name is 1-Bromo-3-methoxy-2-methylbenzene, 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 solution of intermediate 139 (2.5 g, 12.4 mmol) in THF (30 mL) at -70 C was added n-BuLi (1.6 M in hexane) (7.8 mL, 12.4mmol) dropwise over 5 min by syringe along the wall of the flask. After adding, the reaction was stirred at this temperature for 30 min. Then the resulting solution was added into a solution of (S)-tert-butyl 1,6- dioxohexahydropyrrolo[l,2-a]pyrazine-2(lH)-carboxylate (2.0 g, 12 mmol) in THF (30 mL). After stirred at -70C for 5 min, the reaction mixture was quenched with saturated NH4CI and extracted with EtOAc (2 x 20 mL), washed with brine, dried over Na2S04, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography to give the title compound (2 g, yield : 45 %); m/z (ES+) : 377 [M+H]+.

The synthetic route of 31804-36-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; LEO PHARMA A/S; BLADH, Haakon; FELDING, Jakob; ZHOU, Ding; CAI, Zhen-wei; SØRENSEN, Morten Dahl; WO2015/24878; (2015); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Synthetic Route of 349-65-5, 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 349-65-5 as follows.

To a stirring solution of phosgene (1.9 M in toluene; 2.07 mL 0.21 g, 1.30 mmol) in CH2Cl2 (20 mL) at 0 C. was added anh pyridine (0.32 mL) followed by 2-methoxy-5-(trifluoromethyl)aniline (0.75 g). The yellow solution was allowed to warm to room temp during which a precipitate formed. The yellow mixture was stirred for 1 h, then concentrated under reduced pressure. The resulting solids were treated with anh toluene (20 mL) followed by 4-(2-(N-methylcarbamoyl)-4-pyridyloxy)aniline (prepared as described in Method A2; 0.30 g) and the resulting suspension was heated at 80 C. for 20 h, then allowed to cool to room temp. The resulting mixture was diluted with water (100 mL), then was made basic with a saturated NaHCO3 solution (2-3 mL). The basic solution was extracted with EtOAc (2×250 mL). The organic layers were separately washed with a saturated NaCl solution, combined, dried (MgSO4), and concentrated under reduced pressure. The resulting pink-brown residue was dissolved in MeOH and absorbed onto SiO2 (100 g). Column chromatography (300 g SiO2; gradient from 1% Et3N/33% EtOAc/66% hexane to 1% Et3N/99% EtOAc to 1% Et3N/20% MeOH/79% EtOAc) followed by concentration under reduced pressure at 45 C. gave a warm concentrated EtOAc solution, which was treated with hexane (10 mL) to slowly form crystals of N-(2-methoxy-5-(trifluoromethyl)phenyl)-N’-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea (0.44 g): TLC (1% Et3N/99% EtOAc) Rf 0.40.

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; US2003/207872; (2003); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Synthetic Route of 402-52-8, 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. 402-52-8, name is 1-Methoxy-4-(trifluoromethyl)benzene, This compound has unique chemical properties. The synthetic route is as follows.

Example 17 3-14- [3- (2-BENZOYL-4-TRIFLUOROMETHYL-PHENOXY)-BUTOXY]-2-METHYL-PHENYLL-PROPIONIC acid Step A (2-Methoxy-5-trifluoromethyl-phenyl)-phenyl-methanone; A 1.6 M solution of n-BuLi in hexanes (0.51 mL, 0.82 mmol) is added dropwise for about 20 min to N, N, N, N-tetramethylenediamine (0.12 mL, 0. 80 mmol) at -20C UNDER N2 After 20 min, p-trifluoromethylanisole (0.10 g, 0.57 mmol) in THF (0.2 mL) is added dropwise for 15 min at-20 C under N2. After IH, N-methoxy-N-methyl- benzamide (0.12 mL, 0.79 mL) is added dropwise in 10 min AT-20 C UNDERN2. After 2h, a 1 M HCl (0.9 mL) is added. The mixture is extracted with EtOAc, and organic phases are combined and washed with saturated aqueous sodium chloride, and then dried over magnesium sulfate, filtered and concentrated under reduced pressure. Purification by flash chromatography, silica, hexanes: EtOAc (90: 10) provides the title compound (0.09 g, 0.32 mmol, 57%): ES+ (M/E) 281.08 (M+H) + ; RR 0.20 hexanes : EtOAc (90: 10).

The chemical industry reduces the impact on the environment during synthesis 1-Methoxy-4-(trifluoromethyl)benzene. I believe this compound will play a more active role in future production and life.

Reference:
Patent; ELI LILLY AND COMPANY; WO2005/19151; (2005); 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 162705-07-9 as follows. HPLC of Formula: C18H21NO4

General procedure: A mixture of the appropriate piperidine (pyrroline) nitroxyl acids (0.5 mmol), compound 3 (0.5 mmol) and DMAP (20 mg) was stirred in anhydrous CH2Cl2 (20 mL) for 5 min at room temperature under nitrogen. DCC (106 mg, 0.5 mmol) was added and the mixture was stirred for 24 h. The reaction mixture was filtered and the filtrate was evaporated. The residue was subjected to column chromatography on silica gel with CH2Cl2-acetone to afford target compounds 14a-d, and their structures were confirmed from mp, IR, ESR and HRMS analyses.

According to the analysis of related databases, 162705-07-9, the application of this compound in the production field has become more and more popular.

Reference:
Article; Liu, Ying-Qian; Li, Xiao-Jing; Zhao, Chun-Yan; Nan, Xiang; Tian, Jing; Morris-Natschke, Susan L.; Zhang, Zhi-Jun; Yang, Xiao-Ming; Yang, Liu; Li, Lin-Hai; Zhou, Xing-Wen; Lee, Kuo-Hsiung; Bioorganic and Medicinal Chemistry; vol. 21; 5; (2013); p. 1248 – 1256;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Related Products of 36449-75-9, These common heterocyclic compound, 36449-75-9, name is 1-(2-Bromoethyl)-2-methoxybenzene, 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 mixture of the benzyl piperidine intermediate 5 (200 mg,0.770 mmol) and potassium carbonate (266 mg, 1.93 mmol) inMeCN (3.0 mL) was added (2-bromoethyl)benzene (137 muL, 1.00 mmol). After reflux for 24 h, EtOAc (9.0 mL) was added to thereaction mixture and the whole was filtered. The filtrate was evaporatedin vacuo and the residue was purified by silica gel chromatographyusing 0-1% MeOH/CHCl3 as eluent to give 228 mg(90%) of the title compound as a pale yellow solid.

The synthetic route of 36449-75-9 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Yoshinaga, Hidefumi; Masumoto, Shuji; Koyama, Koji; Kinomura, Naoya; Matsumoto, Yuji; Kato, Taro; Baba, Satoko; Matsumoto, Kenji; Horisawa, Tomoko; Oki, Hitomi; Yabuuchi, Kazuki; Kodo, Toru; Bioorganic and Medicinal Chemistry; vol. 25; 1; (2017); p. 293 – 304;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Synthetic Route of 31465-36-8, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 31465-36-8 name is 4-(4-Methoxyphenoxy)aniline, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

General procedure: To a solution of 3-aminobenzensulfoneamide (2.3g, 13.3 mmol) in DMF (12 ml), K2CO3 (3.8 g, 27.0 mmol)and ethylbromoacetate (2.67 g, 16.0 mmol) were added at ambient temperature. The reaction mixture was stirred for 15 hours atroom temperature. The reaction mixture was quenched with sat. NH4Cland extracted with EtOAc. The combined extracts were washed with brine, driedover MgSO4 and evaporated down. Theresidue was purified by silica gel column chromatography to give 2.44 g ofdesired 2h-1 in 71 % yield.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-(4-Methoxyphenoxy)aniline, and friends who are interested can also refer to it.

Reference:
Article; Teno, Naoki; Gohda, Keigo; Wanaka, Keiko; Tsuda, Yuko; Sueda, Takuya; Yamashita, Yukiko; Otsubo, Tadamune; Bioorganic and Medicinal Chemistry; vol. 22; 7; (2014); p. 2339 – 2352;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem