Category: nitriles-buliding-blocks

Synthetic Route of 4421-09-4, A common heterocyclic compound, 4421-09-4, name is 3,4-(Methylenedioxy)benzonitrile, molecular formula is C8H5NO2, 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: A mixture of nitrile (1 mmol), sodium azide (1.5 mmol), catalyst (40 mol%) and DMF (3 mL) was taken in a round-bottomed flask and stirred at 120 C temperature for 12 h. After completion of the reaction the catalyst was separated from the reaction mixture with an external magnet and reaction mixture was treated with ethyl acetate (30 mL) and 5 N HCl (20 mL). The resultant organic layer was separated and the aqueous layer was again extracted with ethyl acetate (20 mL). The combined organic layers were washed with water, concentrated, and the crude material was chromatographed on silica gel (Hexane-EtoAc, 1:1) to afford the pure product. refText

The synthetic route of 4421-09-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Sreedhar; Kumar, A. Suresh; Yada, Divya; Tetrahedron Letters; vol. 52; 28; (2011); p. 3565 – 3569;,
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Electric Literature of 60758-87-4, 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. 60758-87-4 name is 3,4-Diethoxybenzonitrile, 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.

Reference Example 1 In 120 ml of 10% hydrochloric acid-dimethylformamide were dissolved 29 g of 3,4-diethoxybenzonitrile and 23 g of thioacetamide. The solution was heated at 90 C. for 3 hours and further at 130 C. for 5 hours to conduct a reaction. The reaction mixture was subjected to distillation to remove the solvent. The residue was washed twice with 100 ml of diethyl ether, followed by washing with 100 ml of water. The resulting crystals were collected by filtration and dried to obtain 21.7 g of 3,4-diethoxybenzamide. NMR spectrum (DMSO-d6) delta ppm: 1.33(6H, t, J=7 Hz), 4.04(2H, q, J=7 Hz), 4.07(2H, q, J=7 Hz), 6.95(1H, d, J=9.1 Hz), 7.65-7.5(2H, m), 9.30(1H, brs), 9.62(1H, brs)

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3,4-Diethoxybenzonitrile, and friends who are interested can also refer to it.

Reference:
Patent; Otsuka Pharmaceutical Co., Ltd.; US5639770; (1997); A;,
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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. 52516-37-7, name is 2-(3,5-Dichlorophenyl)acetonitrile, A new synthetic method of this compound is introduced below., Safety of 2-(3,5-Dichlorophenyl)acetonitrile

The nitrile was added to a mixture of 40 mL of concentrated sulfuric acid and 50 mL H2O and heated to reflux for 48 hours, cooled to room temperature and stirred for 48 hours. The reaction was diluted into 1 L of crushed ice, warmed to room temperature and extracted with 2*200 mL of dichloromethane and 2*200 mL of ethylacetate. Both sets of organics were combined and washed with saturated aqueous NaHCO3. The NaHCO3 fractions were combined and acidified to pH 1 with 3N HCl. The white solid was too fine to filter and was extracted out with 2*200 mL of dichloromethane. The combined organics were dried with Na2SO4 and the solvents removed at reduced pressure to yield crude 3,5-dichlorophenylacetic acid as a white solid. The solid was slurried with hexane and filtered to get 1.75 g of white solid.

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; Athena Neurosciences, Inc.; Eli Lilly Company; US6506782; (2003); B1;,
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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. 98730-77-9, name is 1-(Hydroxymethyl)cyclopropanecarbonitrile, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 98730-77-9

Thionyl chloride (0.23 mL) was added to a solution of 4-bromo-2-methoxyphenol (209 mg) in toluene (2.0 mL) at room temperature, and the mixture was stirred at 80C for 2 hr. The reaction mixture was concentrated and diluted with DMF (2.0 mL). 4-Bromo-2-methoxyphenol (209 mg) and potassium carbonate (356 mg) were added, and the mixture was stirred at 80C overnight. To the resulting mixture was added brine, and the mixture was extracted with ethyl acetate, dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (165 mg) as a colorless oil. 1H NMR (400 MHz, CHLOROFORM-d) delta 1.06-1.13 (2H, m), 1.31-1.41 (2H, m), 3.85 (3H, s), 3.98 (2H, s), 6.76-6.89 (1H, m), 6.98-7.04 (2H, m).

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 98730-77-9.

Reference:
Patent; Takeda Pharmaceutical Company Limited; KASAI, Shizuo; IGAWA, Hideyuki; TAKAHASHI, Masashi; KINA, Asato; EP2848622; (2015); A1;,
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Adding a certain compound to certain chemical reactions, such as: 50594-78-0, name is 5-Fluoro-2-nitrobenzonitrile, belongs to nitriles-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 50594-78-0, COA of Formula: C7H3FN2O2

To a solution of 5-fluoro-2-nitrobenzonitrile (1 g, 6 mmol) and 3,5- difluorobenzenethiol (1.03 g, 7.05 mmol) in DIVIF (20 mL), was added K2C03 (2.5 g, 18 mmol). The reaction was stirred at 80 C for 1.5 hrs. The residue was poured into H20 (20 mL) and the aqueous phase was extracted with EA (30 mL x2). The organic layer was washed with brine (25 mL), dried over Na2SO4 and concentrated. The residue was purified by silica gel column (PE/EA = 3/1) to give 5-((3,5-difluorophenyl)thio)-2-nitrobenzonitrile (1.4 g, yield: 90%) as a yellow solid.

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, 5-Fluoro-2-nitrobenzonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE; GARDELL, Stephen; PINKERTON, Anthony B.; SERGIENKO, Eduard; SESSIONS, Hampton; (428 pag.)WO2018/132372; (2018); A1;,
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Electric Literature of 873-74-5, These common heterocyclic compound, 873-74-5, name is 4-Aminobenzonitrile, 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: All acyl chloride solutions were freshly prepared in acetonitrile (ACN) at 1 mg/mL. All amine solutions were freshly prepared in water (H2O) at 1mg/mL. A portion of each acyl chloride solution was mixed with an amine solution with an equal volume and the mixture was allowed to stand for about 10 min. Each mixture was diluted with ACN 10-fold for analysis.

The synthetic route of 873-74-5 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Zu, Chengli; Mukhopadhyay, Sukrit; Hanley, Patrick S.; Xia, Shijing; Bell, Bruce M.; Grigg, David; Gilbert, Jeffrey R.; O?Brien, John P.; Journal of the American Society for Mass Spectrometry; vol. 27; 5; (2016); p. 917 – 926;,
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Reference of 94088-46-7, A common heterocyclic compound, 94088-46-7, name is 2-Fluoro-6-methoxybenzonitrile, molecular formula is C8H6FNO, 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.

Step 1 : A solution of 2-fluoro-6-methoxybenzonitrile (10 g, 66.2 mmol) in (0490) trifluoromethanesulfonic acid (100 mL) at 0C was treated with N-bromosuccinimide (12.4 g, 69.5 mmol) and the mixture was allowed to warm to RT and was stirred for 3 days. The reaction mixture was cooled to 0 C, quenched with ice, and made basic with 6 M KOH, and the resulting solid was collected by filtration. The filter cake was dissolved in ethyl acetate and dried over sodium sulfate, and the mixture was filtered. The filtrate was concentrated to afford an approximately 1 :1 mixture of 3-bromo-6-fluoro-2-methoxybenzonitrile and 3-bromo-2-fluoro- 6-methoxybenzonitrile, which was used in the next step without purification or analysis.

The synthetic route of 94088-46-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS AG; BURSULAYA, Badry; FISCH, Andreas; LAJINESS, James Paul; MACHAUER, Rainer; MALEKAR, Swapnil; PETRASSI, Hank Michael James; RAMAZANI, Farshad; REMOND, Anne-Catherine; ULLRICH, Thomas; USSELMANN, Peggy; VANGREVELINGHE, Eric; (145 pag.)WO2018/55550; (2018); A1;,
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14447-18-8, name is Benzyl cyanoacetate, belongs to nitriles-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. Computed Properties of C10H9NO2

A. 2-Cyano-4-ethyl-hex-2-enoic acid benzyl ester To a mixture of 2-ethylbutyraldehyde (2.0 mL, 16.2 mmol) and benzyl cyanoacetate (2.85 g, 16.2 mmol) at 0 C. was added acetic acid (0.1 mL, 1.62 mmol), then piperidine (0.16 mL, 1.62 mmol) dropwise. The ice bath was removed, and stirring continued for 10 minutes. Additional acetic acid (0.1 mL) and piperidine (0.16 mL) were added, followed by the additional of oven-dried 4A molecular sieves such that stirring was not impeded. The mixture was stirred 1.5 h, then partitioned between EtOAc and sat. NaHCO3 (aq). The phases were separated, and the organic phase washed with brine, dried (MgSO4), and concentrated to provide 3.96 g (95%) of 2-cyano-4-ethyl-hex-2-enoic acid benzyl ester as a colorless oil. 1H NMR (CDCl3) delta 7.39 (m, 6H), 5.28 (s, 2H), 2.60 (m, 1H), 1.62 (m, 2H), 1.40 (m, 2H), 0.88 (t, J=7.6 Hz, 6H). 13C NMR delta 168.69, 161.40, 135.01, 128.90, 128.82, 128.50, 114.11, 109.94, 68.07, 46.35, 27.30, 11.95. IR (neat) 2233, 1729 cm-1. LRMS: m/z 256.1 (M-1). Anal. Calcd for C16H19NO2: C, 74.68; H, 7.44; N, 5.44. Found: C, 74.75; H, 7.52; N, 5.50.

The synthetic route of 14447-18-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Schwarz, Jacob Bradley; Wustrow, David Juergen; US2004/147608; (2004); A1;,
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120315-65-3, name is 4-Bromo-3-methoxybenzonitrile, belongs to nitriles-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. Recommanded Product: 120315-65-3

Step 1: tert-Butyl (1-(4-((4-cyano-2-methoxyphenyl)ethynyl)phenyl)cyclobutyl)carbamate: To a solution of 4-bromo-3-methoxybenzonitrile (1.92 g, 7.075 mmol) in anhydrous triethylamine (8 mL) and 1 ,4-dioxane (8 mL) was added bis(tert- butylphosphine)palladium(O) (0.144g, 0.283mmol) and copper(l) iodide (13 mg,0.094mmol). The reaction mixture was then degassed with N2 for 10 minutes before being cooled to 0C. A solution of ferf-butyl 1 -(4-ethynylphenyl)cyclobutylcarbamate (1.00 g, 4.72 mmol) in TEA (8 mL) was added dropwise to the cooled reaction mixture. The reaction was allowed to warm to RT and stirred for 18 hours. The reaction mixture was concentrated in vacuo and the residue diluted with DCM (20 mL) and filtered through Celite. The resulting filtrate was concentrated in vacuo to afford a brown oil that was purified by silica gel chromatography (ethyl acetate/hexane gradient, 0?50%) yielding the title compound as an off-white solid (890 mg, 47%). 1H NMR (500 MHz, CDCI3): delta 7.55-7.53 (m, 3H), 7.43 (d, 2H), 7.23 (d, 1 H), 7.12 (s, 1 H), 5.25 (s, 1 H), 3.94 (s, 3H), 2.54-2.51 (m, 4H), 2.1 1-2.13 (m, 1 H), 1.90-1.86 (m, 1 H), 1.34-1.25 (br s, 9H).

The synthetic route of 120315-65-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ALMAC DISCOVERY LIMITED; BELL, Mark, Peter; O’DOWD, Colin, Roderick; ROUNTREE, James, Samuel, Shane; TREVITT, Graham, Peter; HARRISON, Timothy; MCFARLAND, Mary, Melissa; WO2011/55115; (2011); A1;,
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Application of 5332-06-9, 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. 5332-06-9, name is 4-Bromobutanenitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To a solution of ethyl 2-(benzylamino)acetate (50 g, 258.7 mmol) and K2C03 (71.5 g, 517.5 mmol) in MeCN (500 mL) was added 4-bromobutyronitrile (28.7 mL, 284.6 mmol)dropwise. The mixture was heated to 80 C for 12 h under a nitrogen atmosphere. After cooling to room temperature, the mixture was filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography (petroleum ether / EtOAc = 5 : 1) to give the title compound (56 g, 83%) as light yellow oil. ?H NMR (400 IVIFIz, CDC13) 7.37 – 7.28 (m, 5H),4.18 (q, J 7.2 Hz, 2H), 3.80 (s, 2H), 3.32 (s, 2H), 2.80 (t, J= 6.4 Hz, 2H), 2.47 (t, J= 7.2 Hz,2H), 1.87 – 1.77 (m, 2H), 1.29 (t, J= 7.2 Hz, 3H).

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

Reference:
Patent; GENENTECH, INC.; CONSTELLATION PHARMACEUTICALS, INC.; CYR, Patrick; BRONNER, Sarah; ROMERO, F. Anthony; MAGNUSON, Steven; TSUI, Vickie Hsiao-Wei; MURRAY, Jeremy M.; WAI, John; LAI, Kwong Wah; WANG, Fei; CHEN, Kevin X.; (351 pag.)WO2017/205538; (2017); A1;,
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