Author: Jessica.F

Synthetic Route of 38380-85-7, 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. 38380-85-7 name is 1-Bromo-4-cyclopropoxybenzene, 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: A mixture of 2,4-dibromothiazole (Compound 8A) (3.9 g, 16 mmol), 3,4- dichlorophenylboronic acid (3.05 g, 16 mol), Pd(dppf)C12 (0.7 g, 0.87 mmol), and cesium carbonate (15 g, 46 mmol) in DME (120 mL) and water (10 mL) was heated at reflux under nitrogen overnight. The reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (200 mL x 2). The combined extracts were washed with water (200 mL) and brine (200 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified with flash column chromatography on silica gel (ethyl acetate in petroleum ether, from 0% to 10% v/v) to yield Compound 8B. LC-MS (ESI) m/z: 308 [M+H]t

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Bromo-4-cyclopropoxybenzene, and friends who are interested can also refer to it.

Reference:
Patent; BIOMARIN PHARMACEUTICAL INC.; WANG, Bing; CHAO, Qi; (737 pag.)WO2019/133770; (2019); A2;,
Ether – Wikipedia,
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Electric Literature of 651734-54-2, A common heterocyclic compound, 651734-54-2, name is 2,6-Difluoro-3,5-dimethoxyaniline, molecular formula is C8H9F2NO2, 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 2-L reactor equipped with a thermocouple, a nitrogen inlet and mechanical stirrer were charged AOV-dimethyl formamide (450 mL, 425 g), 4-chloro-2-(morpholinomethyl)-l- (phenylsulfonyl)- 1 //-pyrrolo|2.3-6 |pyridine-5-carbaldehyde (30.0 g, 71.45 mmol) and 2,6- difluoro-3,5-dimethoxyanihne (14.2 g, 75.0 mmol). To this suspension (internal temperature 20 C) was added chlorotrimethylsilane (19.4 g, 22. 7 mL, 179 mmol) dropwise in 10 min at room temperature (internal temperature 20-23 C). The suspension changed into a solution in 5 min after the chlorotrimethylsilane addition. The solution was stirred at room temperature for 1.5 h before cooled to 0-5 C with ice-bath. Borane-THF complex in THF (1.0 M, 71.4 mL, 71.4 mmol, 64.2 g, 1.0 eq.) was added dropwise via additional funnel over 30 min while maintaining temperature at 0-5 C. After addition, the mixture was stirred for 4 h. Water (150 g, 150 mL) was added under ice-bath cooling in 20 min, followed by slow addition of ammonium hydroxide solution (28% N, 15.3 g, 17 ml, 252 mmol, 3.53 eq.) to pH 9-10 while maintaining the temperature below 10 C. More water (250 mL, 250 g) was added through the additional funnel. The slurry was stirred for 30 min and the solids were collected by filtration. The wet cake was washed with water (90 g x 2, 90 ml x 2) and heptane (61.6 g x2, 90 ml x 2). The product w as suction dried overnight to give the desired product LG-((4- chloro-2-(morphohnomethyl)-l-(phenylsulfonyl)-li/-pyrrolo[2,3-Z>]pyridin-5-yl)methyl)-2,6- difluoro-3,5-dimethoxyaniline (41.6 g, 96% yield): LCMS calculated for C27H28ClF2N405S[M+H]+: 593.10; Found: 593.1 ; NMR (400 MHz, DMSO-d6) 5 8.36 (m, 2H), 8.28 (s, 1H), 7.72 (m, 1H), 7.63 (m, 2H), 6.78 (s, 1H), 6.29 (m, 1H), 5.82 (m, 1H), 4.58 (m, 2H), 3.91 (s, 2H), 3.76 (s, 6H), 3.56 (m, 4H), 2.47 (m, 4H).

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; INCYTE CORPORATION; BURN, Timothy C.; LIU, Phillip C.; FRIETZE, William; JIA, Zhongjiang; TAO, Ming; WANG, Dengjin; ZHOU, Jiacheng; LI, Qun; (262 pag.)WO2019/213544; (2019); A2;,
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These common heterocyclic compound, 10541-78-3, name is 2-Methoxy-N-methylaniline, 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. HPLC of Formula: C8H11NO

To a stirring dichloromethane (40 mL) solution containing 5-bromo-4- chloro-2-hydroxybenzoic acid (2.0 g, 8.0 mmol), were added triethylamine (2.2 mL, 16.0 mmol), HATU (4.5 g, 12 mmol) and 2-methoxyl-N-methylaniline (1.19 g, 8.7 mmol). The mixture was stirred at rt for 16 hrs and water was added. The organic layer was separated, washed with NaHCO3, dried over Na2SO4, filtered and concentrated. The residue was purified via silica gel flash column chromatography eluting with 20% ethyl acetate in hexane to afford 5-bromo-4-chloro-2-hydroxy-N-(2- methoxy-phenyl)-N-methyl-benzamide (300 mg). MS [M+H]+: 371.9; tR = 2.60 min (method 1)Alternatively, a mixture of 5-bromo-4-chloro-2-hydroxybenzoic acid (5 g, 19.9 mmol), 2-methoxy-N-methyaniline (3.13g, 22.9 mmol) and P2O5 (5.36g, 37. 8 mmol) in anhydrous xylene was heated at 60 0C for 2 hrs and then refluxed for 17 hrs. The mixture was concentrated and purified via silica gel flash column chromatography eluted with ethyl acetate in hexane (20%) to give 5-bromo-4-chloro-2-hydroxy-N-(2- methoxy-phenyl)-N-methyl-benzamide (3.3 g).

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

Reference:
Patent; NEUROCRINE BIOSCIENCES, INC.; WO2008/124610; (2008); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

7664-66-6, name is 4-Isopropoxyaniline, 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. HPLC of Formula: C9H13NO

To a solution of 4-isopropoxyaniline (9.06 g, 60.0 mmol) in CH2Cl2 (120 mL) and pyridine (30 mL) was added 4-nitrophenyl chloroformate (10.9 g, 54.0 mmol) portionwise with stirring over ~1 min with brief ice-bath cooling. After stirring at room temperature for 1 h, the homogeneous solution was diluted with CH2Cl2 (300 mL) and washed with 0.6 M HCl (1*750 mL) and 0.025 M HCl (1*1 L). The organic layer was dried (Na2SO4) and concentrated to give the title compound as a light violet-white solid (16.64 g, 98%). 1H NMR (CDCl3) delta 8.31-8.25 (m, 2H), 7.42-7.32 (m, 4H), 7.25-7.20 (m, 2H), 6.93 (br s, 1H), 2.90 (sep, J=6.9 Hz, 1H), 1.24 (d, J=6.9 Hz, 6H). LC/MS (ESI) calcd for C16H17N2O5 (MH)+ 317.1, found 633.2 (2 MH)+.

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; US2006/281700; (2006); A1;,
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Reference of 33170-72-8, 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 33170-72-8 as follows.

2-Bromo-1,1-dimethoxypropane (2a) (18 g, 98.34 mmol) was dissolved in chloroform (100 mL), trifluoroacetic acid (67.28 g, 590.03 mmol) was added and reacted at room temperature for 4 hours. The reaction solution was added with dichloromethane (30 mL) and water (15 mL), and the layers were extracted.The organic phase was washed with saturated brine (100 mL x 4), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure at 30 C to give the title compound 2b as a yellow liquid (5 g, 37% yield).

According to the analysis of related databases, 33170-72-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Sichuan Hai Sike Pharmaceutical Co., Ltd.; Wei Yonggang; Qiu Guanpeng; Lei Bolin; Li Yao; Wang Song; Zhu Guozhi; (39 pag.)CN106279128; (2017); A;,
Ether – Wikipedia,
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These common heterocyclic compound, 50742-37-5, name is (3-Phenoxyphenyl)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. Safety of (3-Phenoxyphenyl)methanamine

To a solution of 3-phenoxybenzylamine described in Preparation Example 4 (33mg, 0.167mmol) and benzothiazole-6-carboxylic acid (30mg, 0.167mmol) in tetrahydrofuran (1 mL) were added benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (89mg, 0.20mmol) and triethylamine (28mul, 0.20mmol), and the solution was stirred at room temperature for 17 hours. The solvent was evaporated, the residue was purified by NH silica gel column chromatography (hexane : ethyl acetate), and the title compound (37mg, 62%) was obtained as a colorless oil. 1H-NMR Spectrum (CDCl3) delta(ppm) : 4.68(2H, d, J=6.0Hz), 6.50(1H, brs), 6.94(1H, dd, J=2.0, 8.0Hz), 7.02-7.04(3H, m), 7.11-7.15(2H, m), 7.31-7.37(3H, m), 7.88(1H, dd, J=1.6, 8.8Hz), 8.18(1H, d, J=8.8Hz), 8.49(1H, d, J=1.6Hz), 9.13(1H, s).

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

Reference:
Patent; Eisai Co., Ltd.; EP1669348; (2006); A1;,
Ether – Wikipedia,
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Synthetic Route of 2062-98-8,Some common heterocyclic compound, 2062-98-8, name is Perfluoro(2-methyl-3-oxahexanoyl) fluoride, molecular formula is C6F12O2, 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.

In the first step, the fluoroalkyl alcohol was prepared from 2-trifluoromethyl-3-oxa-2,4,4,5,5,6,6,6-octafluorohexanoyl fluoride (i.e. HFPO dimer, commercially available from DuPont). In a reaction flask equipped with condenser and temperature probe was charged LiAlH4 (13.5 g, 0.355 moles) and 500 ml ether solvent and the contents cooled to 0 C. (NaBH4 may be employed in place of LiAlH4). HFPO-dimer (149.4 g, 0.45 moles) was added slowly and the reaction flask contents temperature was controlled at <10 C. with external cooling. After the addition was completed, the reaction mixture was stirred for 2-3 hours at 5-10 C. The reaction mixture was slowly transferred into a 400 ml 6 N HCl/500 mL ice water mixture and the ether layer was separated. The bottom layer was extracted with 200 mL ether (twice). The ether layers were combined, dried over magnesium sulfate, and then distilled to give the fluoroalcohol 2-trifluoromethyl-3-oxa-2,4,4,5,5,6,6,6-octafluorohexane-1-ol (HFPO dimer alcohol) as a clear, colorless liquid, Bp. 112-114 C. Yield: 127 grams (89%).1H-NMR (400 MHz, acetone-d6): delta4.30 (m); 19F-NMR (376.89 MHz, acetone-d6): -80.5 to -82.5 (m, 8F), -129.4 (m, 2F), -134.6 (dm, 1F). These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Perfluoro(2-methyl-3-oxahexanoyl) fluoride, its application will become more common. Reference:
Patent; DUPONT PERFORMANCE ELASTOMERS LLC; US2011/257423; (2011); A1;,
Ether – Wikipedia,
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Electric Literature of 150-78-7,Some common heterocyclic compound, 150-78-7, name is 1,4-Dimethoxybenzene, molecular formula is C8H10O2, 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.

Silfen was freshly prepared by thoroughly grindingFe(NO3)3(H2O)9 (2.0 g) and silica gel (4.0 g; 230-400 mesh) in a mortar [2]. A 25 mLround-bottomed flask was charged with 600 mg of silfen, iodine (142 mg; 1.1 mmol),1,4-dimethoxybenzene (138 mg; 1.0 mmol) and CH2Cl2 (2 mL), and the mixture wasstirred at 25 C overnight. The product was isolated by partitioning the reaction mixturebetween ethyl acetate and water, followed by washing the organic layer with 5% aqsodium thiosulfate and water, and drying (Na2SO4). Concentration by rotary evaporationgave an oil which was purified by CombiFlash chromatography (silica gel; 0-30%CH2Cl2 in hexane over 20 min) to afford a colourless oil (161 mg; 61%). 1H-NMR(CDCl3, 500 MHz): 3.74 (s, 3H, OCH3), 3.81 (s, 3H, OCH3), 6.74 (d, 1H, J = 8.8 Hz, H-6), 6.85 (dd, 1H , J = 8.8, 3.1 Hz, H-5), 7.30 (d, 1H, J = 3.1 Hz, H-3). 13C-NMR (CDCl3,125 MHz): 56.0, 57.1, 86.2, 111.7, 114.7, 125.0, 152.7, 154.3.

The synthetic route of 150-78-7 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Kempton, Robert J.; Kidd-Kautz, Taylor A.; Laurenceau, Soizic; Paula, Stefan; Beilstein Journal of Organic Chemistry; vol. 15; (2019); p. 971 – 975;,
Ether – Wikipedia,
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Adding a certain compound to certain chemical reactions, such as: 458-52-6, name is 2-Fluoro-4-methoxyaniline, 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 458-52-6, category: ethers-buliding-blocks

Step C 2-Fluoro-4-methoxyphenyl isocyanate To a solution of 13.75 g (0.0967 mole) of 2-fluoro-4-methoxyaniline in 120 mL of toluene was slowly added over a period of 30 minutes a solution of 19.13 g (0.0967 mole) of trichloromethyl chloroformate in 30 mL of toluene. During the addition the temperature rose to 35° C. The reaction mixture was stirred without external heating for 30 minutes and then heated at reflux for approximately 17 hours. At the end of this time all of the solvent was removed by distillation, leaving 2-fluoro-4-methoxyphenyl isocyanate as a purple liquid, which was used immediately in Step D.

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-4-methoxyaniline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; FMC Corporation; US5262390; (1993); A;,
Ether – Wikipedia,
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These common heterocyclic compound, 645-36-3, name is 2,2-Diethoxyethanamine, 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 2,2-Diethoxyethanamine

(1-1) Synthesis of Compound 1 1-naphthaldehyde (Wako Pure Chemical Industries, Ltd.)(1.56 g, 10 mmol) and 2,2-diethoxyethanamine (TOKYO CHEMICAL INDUSTRY CO., LTD.)(1.33 g, 10 mmol) were mixed and stirred at 100C for 20 min. After the mixture was cooled to room temperature, EtOH (20 mL) was used for dilution. NaBH4 (0.38 g, 10 mmol) was added dropwise and the mixture was stirred at room temperature for 16 h. After completion of the reaction, EtOH was distilled away under reduced pressure. Then, a product was extracted with AcOEt. The resulting product was purified by silica gel column chromatography (hexane/AcOEt = 5/1) to yield compound 1 (2.29 g, 8.5 mmol, 85%).

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

Reference:
Patent; National University Corporation Tottori University; Tokyo Women’s Medical University; SHIOTA, Goshi; HOSHIKAWA, Yoshiko; MATSUMOTO, Noriko; MATSUMI, Yoshiaki; MORIMOTO, Minoru; TONOI, Takayuki; SAIMOTO, Hiroyuki; OHASHI, Kazuo; OKANO, Teruo; EP2698365; (2014); A1;,
Ether – Wikipedia,
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