Month: June 2021

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. 64248-64-2, name is 2,5-Difluorobenzonitrile, A new synthetic method of this compound is introduced below., Computed Properties of C7H3F2N

26.1 4-(2-Cyano-4-fluoro-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester The title compound was prepared a follows. 2-5-Difluorobenzonitrile (1.00 g, 7.2 mmol) was added at room temperature to a stirred mixture under argon of sodium hydride (55%, 207 mg, 9 mmol) in dimethylformamide (DMF) (10 ml). 4-Hydroxypiperidine-1-carboxylic acid tert-butyl ester (3.32 g, 17 mmol) was added in portions. The resulting mixture was stirred several hours at 50 C. before partitioning it between H2O and ethyl acetate (EtOAc). The organic layer was washed with sat. aq. NH4Cl sol. and brine and dried over MgSO4. Evaporation of the solvent yielded 2.24 g (97.2%, 7 mmol) of a light brown solid. MS (m/z): 321.1 (M+H+).

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; Gobbi, Luca Claudio; Jaeschke, Georg; Roche, Olivier; Rodriguez Sarmiento, Rosa Maria; Steward, Lucinda; US2008/103174; (2008); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Electric Literature of 654-70-6, 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. 654-70-6 name is 4-Cyano-3-trifluoromethylaniline, 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.

1) Preparation of 4-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-trifluoromethylbenzonitrile (1.1) Compound 1.1 can be prepared by process “A”. To this end, 14.74 g (79.21 mmol) of 4-amino-2-trifluoromethylbenzonitrile were dissolved in 200 ml of dry acetonitrile. This solution was added dropwise with stirring to a 20% solution, heated to 70 C., of phosgene in toluene and then stirred for 1 h. The cooled reaction solution was concentrated under reduced pressure, and the residue was taken up with toluene and concentrated again under reduced pressure. Finally, the residue was dissolved in 150 ml of dry acetonitrile and the solution was admixed with 15.5 g (79.21 mmol) of tert-butyl 2-amino-2-methylpropionate hydrochloride with stirring. 12.02 g (118.8 mmol) of triethylamine were slowly added dropwise to the reaction mixture which was then stirred at room temperature for 45 min. Thereafter, the mixture was admixed cautiously with 50 ml of concentrated hydrochloric acid and stirred at 70 C. for 1 h. The cooled reaction mixture was concentrated under reduced pressure and the residue was admixed with ethyl acetate and water. The organic phase was removed, washed with saturated sodium carbonate solution and then with water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on silica gel with 2:1 heptane/ethyl acetate. 21.2 g (90% yield) of 4-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-trifluoromethylbenzonitrile 1.1 with the melting point of 208-211 C. were obtained. ; 1) Preparation of 4-(2,4-dioxo-1,3-diazaspiro[4.5]dec-3-yl)-2-trifluoromethylbenzonitrile (28.1) Compound 28.1 can be prepared by process “A”. To this end, 5.3 ml of phosgene solution (20% in toluene) were initially charged under argon atmosphere. At 75 C., a solution of 4-cyano-3-trifluoromethylaniline in 15 ml of dry acetonitrile was slowly added dropwise. After the addition had ended, the mixture was stirred at 75 C. for another 90 min. The mixture was concentrated under reduced pressure. The residue was then taken up repeatedly in toluene and concentrated again under reduced pressure. Finally, the residue was dissolved in 15 ml of dry tetrahydrofuran, admixed with 0.72 g of 1-amino-1-cyclohexanecarboxylic acid and dropwise with 1.05 ml of triethylamine, and the mixture was stirred at room temperature for 2 h. After standing overnight at room temperature, the reaction mixture was admixed with 5 ml of concentrated hydrochloric acid and stirred under reflux for 2 h. The cooled reaction mixture was admixed with saturated sodium hydrogencarbonate solution and extracted with ethyl acetate. The organic phase was dried over magnesium sulfate, filtered and concentrated under reduced pressure. 0.62 g of 4-(2,4-dioxo-1,3-diazaspiro[4.5]dec-3-yl)-2-trifluoromethylbenzonitrile (28.1) was obtained. 1H NMR: 9.21, s, 1H, 8.30, d, 1H, 8.19, s, 1H, 8.02, d, 1H, 1.8-1.5, m, 9H, 1.4-1.25, m, 1H.

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

Reference:
Patent; SANOFI-AVENTIS; US2009/215728; (2009); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Some common heterocyclic compound, 36282-26-5, name is 2-Bromo-4-fluorobenzonitrile, molecular formula is C7H3BrFN, 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. Quality Control of 2-Bromo-4-fluorobenzonitrile

Example 10 4-fluoro-2-(1H-pyrrolo[2,3-b]pyridin-4-ylethynyl)benzonitrile Dichloro bis(triphenylphosphine) palladium (II) (29.6 mg, 0.0422 mmol), and triethylamine (742 mul, 534 mg, 5.28 mmol) were added to a solution of intermediate 10.2 (150 mg, 1.06 mmol) and 2-bromo-4-fluorobenzonitrile (1.06 g, 5.28 mmol) in 1,4-dioxane (4 mL), and placed in a sealable tube. Nitrogen gas was bubbled in the reaction mixture for 5 min, before the tube was sealed and the reaction mixture was heated at 80 C. for 2 h. After cooling, the brown solution was filtered through Celite and concentrated under vacuo. The residue was purified by chromatography on a SP1 Biotage system, using hexanes and ethyl acetate as eluents to afford the title compound (33 mg, 12%) as a yellow solid (HPLC: 99%, RT: 6.20 min) 1H NMR (DMSO-d6) delta=12.05 (br s, 1H), 8.31 (d, J=5.1 Hz, 1H), 8.13 (dd, J=8.8, 5.5 Hz, 1H), 7.90 (dd, J=9.3, 2.6 Hz, 1H), 7.69 (dd, J=3.3, 2.6 Hz, 1H), 7.59 (td, J=8.4, 2.6 Hz, 1H), 7.27 (d, J=4.8 Hz, 1H), 6.78 (dd, J=3.7, 1.8 Hz, 1H); MS (m/z) 262 [M+H]+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 36282-26-5, its application will become more common.

Reference:
Patent; MERCK PATENT GMBH; US2011/282056; (2011); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

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 2042-37-7 as follows. HPLC of Formula: C7H4BrN

General procedure: In 50 mL round bottom flask, aryl halide (1.0 mmol), pyrazole (1.2 mmol), ligand (0.04 mmol), Cu2O (0.10 mmol), cesium carbonate (2.0 mmol), and dry solvent (20 mL) were placed under nitrogen atmosphere. The reaction mixture was heated in oil bath up to specified temperature under constant stirring for 20 h and then allowed to cool to room temperature. The reaction mixture was filtered through a plug of Celite in a fritted filter funnel and washed with ethyl acetate. If DMSO is used as solvent, it is extracted by washing the filtrate with 25 mL water for three times. The organic phase was dried over anhydrous MgSO4 and was removed under reduced pressure to provide the crude product which was purified by column chromatography on silica gel, using hexane and ethyl acetate in 3:1 ratio, respectively, as an eluent.

According to the analysis of related databases, 2042-37-7, the application of this compound in the production field has become more and more popular.

Reference:
Article; Damkaci, Fehmi; Alawaed, Abdulkhaliq; Vik, Erik; Tetrahedron Letters; vol. 57; 20; (2016); p. 2197 – 2200;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

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. 628-20-6, name is 4-Chlorobutyronitrile belongs to nitriles-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Recommanded Product: 628-20-6

K2CO3 663.40g (4.8mol), KI 26.60g (0.16mol),1-(2-methoxy-phenyl)piperazine hydrochloride 457.40 g (2.0 mol),After adding 1500 mL of acetonitrile, 52.70 g (2.4 mol) of 4-chlorobutyronitrile was added dropwise with stirring at 70 C, and after 44.5 h of reaction, the reaction was completed on the spot plate. stop,In order to avoid solid precipitation of [4-(2-methoxyphenyl) piperazinyl]butyronitrile,The mixture was washed with hot water, and the solid was washed well with acetonitrile.Wash the solid slightly with a mixed solvent of acetone and petroleum ether.The mother liquor is evaporated to dryness and then recrystallized with a small amount of acetone petroleum ether.A total of 466.8 g of a white solid was obtained in a total of 90.0% yield.

The synthetic route of 628-20-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; The Chinese People’s Liberation Army Military Academy Of Medical Sciences Poison Pharmaceutical Institute; Li Jin; Yang Rifang; Song Rui; Wu Ning; Li Yunfeng; Wang Weina; Song Dake; (26 pag.)CN109419802; (2019); A;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Some common heterocyclic compound, 1009-35-4, name is 4-Fluoro-3-nitrobenzonitrile, molecular formula is C7H3FN2O2, 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: C7H3FN2O2

To a solution of 4-fluoro-3-nitrobenzonitrile (300 mg) and dimethyl malonate (286 mg) in DMF was added 60percent NaH at 0°C, followed by reaction at room temperature to obtain dimethyl (4-cyano-2-nitrophenyl)malonate (198 mg).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1009-35-4, its application will become more common.

Reference:
Patent; Astellas Pharma Inc.; EP2003132; (2008); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Synthetic Route of 59997-51-2, A common heterocyclic compound, 59997-51-2, name is 4,4-Dimethyl-3-oxopentanenitrile, molecular formula is C7H11NO, 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.

The cyanoxime ligand was obtained according to the modified procedure described by Fedorenko [38] using the pivaloylacetonitrile, NC-CH2-C(O)C(CH3)3, as starting material. Thus, 4.06 g (3.24 mM) of the latter were dissolved in 75 mL of CH3OH to which 2.46 g (3.57 mM; 1.10 times excess with respect to the acetonitrile) of NaNO2 in 150 mL of H2O were added. Then 2.80 mL of glacial acetic acid were added dropwise within 2 h; this mixture precooled to -2 C under the N2 blanket. The mixture was allowed to stay overnight at 0 C and then 100 mL of water and 5 drops of HCl (conc.) were added at once, which resulted in the mixture discoloration and the quick formation of the HPiCO as a white precipitate.The latter was filtered, washed twice with 10 mL ofwater and dried in a desiccator under vacuum, yielding 3.54 g ofthe cyanoxime. An additional portion of 1.07 g of HPiCO can berecovered from the mother liquor using extraction with 3 portions(50 mL each) of ether. The combined total yield is 92% (4.61 g); the compound melts at 150 C followed by rapid decomposition. TheNMR spectra in dmso-d6 (ppm): 1H – 14.88 (1H, slightly broadenedsinglet, oxime), 1.28 (9H, singlet, three methyl groups); 13C – 198.17(CO), 132.10 – oxime, 109.19 (CN), 44.29 – C(CH3)3, 27.03-methylgroups. The bands in the IR-spectrum (KBr, cm1): 3275, strong – m(OH); 2985, 2944, 2924, 2877 all medium – mas, ms (CH); 2231, weak- m (C?N); 1674, strong – m (CO); 1590, weak – m (CN); 1054,1030, strong – m (NAO). The compound represents a whitecrystalline solid not soluble in water, sparingly soluble in hexaneand cyclohexane, and well soluble in alcohols, acetone andchlorohydrocarbons.

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:
Article; Mann, Alexandra; Gerasimchuk, Nikolay; Silchenko, Svitlana; Inorganica Chimica Acta; vol. 440; (2016); p. 118 – 128;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Adding a certain compound to certain chemical reactions, such as: 394-47-8, name is 2-Fluorobenzonitrile, 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 394-47-8, Safety of 2-Fluorobenzonitrile

To a suspension of2-fluorobenzonitrile (10.0 g, 82.6 mmol) and phenol (7.7g,5.1 mmol) in DMF (80 mL) was added K2C03 (22.8 g, 165 mmol) at rt. The reaction was stirred at 130 oc for 10 h. The reaction mixture was diluted with water, extracted with EtAOAc (100 mLx3), washed with brine (100 mL), dried (Na2S04), and concentrated togive 15.0 g, (93%) of the title compound as a yellow oil. 1NMR (400 MHz, CDCh): 8 6.85 (1H, d, J = 8.4 Hz), 7.07-7.14 (3H, m), 7.22 (1H, t, J = 7.2 Hz), 7.40 (2H, t, J = 8.0Hz), 7.47 (1H, td, J = 2.0, 8.4 Hz), 7.65 (1H, dd, J = 1.2, 8.0 Hz).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Fluorobenzonitrile, and friends who are interested can also refer to it.

Reference:
Patent; QUANTICEL PHARMACEUTICALS, INC.; CHEN, Young, K.; KANOUNI, Toufike; NIE, Zhe; STAFFORD, Jeffrey, Alan; VEAL, James, Marvin; WALLACE, Michael, Brennan; WO2014/100818; (2014); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

425379-16-4, name is 2-Bromo-3-fluorobenzonitrile, 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: 2-Bromo-3-fluorobenzonitrile

To a solution of 2-bromo-3-fluorobenzonitrile (10.0 g, 50 mmol) in sulfuric acid (22 mL) was added nitric acid (69%, 4.82 mL, 75 mmol) dropwise, maintaining the temperature between 5-10 C. The reaction mixture turned red-orange at the end of the addition. The reaction mixture was allowed to warm up to RT and was stirred for 1 hour. The reaction mixture was then poured onto crushed ice. The products were extracted with EtOAc (2 x 100 mL). The combined organic layers were washed with brine (50 mL), dried (MgS04), filtered and concentrated under reduced pressure. The residue was suspended in MeOH (50 mL) and the mixture was briefly heated at reflux. After cooling to RT, a pale yellow precipitate was collected by vacuum filtration, washed with a small amount of MeOH and dried in the vacuum oven. The material was recrystallized from MeOH to afford 1 .77 g (14% yield) of the title compound as a yellow powder.1H NMR (500 MHz, DMSO-d6) delta [ppm] 8.77 (dd, J = 2.5, 1 .4 Hz, 1 H), 8.65 (dd, J = 8.3, 2.5 Hz, 1 H).LCMS (Analytical Method A): Rt = 1 .1 1 min, mass ion not observed.

The synthetic route of 425379-16-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; BAeURLE, Stefan; DAVENPORT, Adam, James; STIMSON, Christopher; CARR, James, Lindsay; BUBERT, Christian, Abingdon; MARLIN, Frederic, Jacques; NAGEL, Jens; SCHMIDT, Nicole; ROTGERI, Andrea; IRLBACHER, Horst; (378 pag.)WO2018/114783; (2018); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Related Products of 6330-25-2, 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. 6330-25-2 name is 2-Cyano-N-methyl-acetamide, 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.

9.6: 7-Amino-2-chloro-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic Acid Methylamide; In a 250 ml round-bottomed flask, under a nitrogen atmosphere, 1.3 g (33.0 mmol) of NaH at 60% are suspended in 35 ml of anhydrous DMF. The temperature of the mixture is reduced to 0 C. by means of an ice bath. 1.6 g (16.5 mmol) of 2-cyano-N-methylacetamide are added and the mixture is then stirred for 15 min at 0 C. and 1 h at ambient temperature. The temperature of the mixture is reduced to 0 C. by means of an ice bath, before said mixture is added dropwise to a solution, at 0 C., of 3.2 g (15.8 mmol) of the compound of stage 9.5 dissolved in 35 ml of DMF. The mixture is stirred for 2 hours at ambient temperature and then 660 mg (16.5 mmol) of NaH at 60% are added. The stirring of the mixture is continued for 2 h at ambient temperature and then the mixture is poured into ice-cold water (50 ml) and the DMF is evaporated off under reduced pressure. The precipitate formed is filtered off and washed with water (2×25 ml) and the resulting product is dried in an oven, so as to obtain 2.3 g (8.4 mmol) of compound in the form of a white powder. Yield=53%. 1H NMR DMSO d6 (300 MHz): 1.23 (t, J=7.1 Hz, 3H); 2.80 (d, J=4.7 Hz, 3H); 4.34 (q, J=7.1 Hz, 2H); 8.42 (bs, 1H); 9.11 (s, 1H); 10.71 (d, J=4.7 Hz, 1H); 11.96 (bs, 1H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Cyano-N-methyl-acetamide, and friends who are interested can also refer to it.

Reference:
Patent; SANOFI-AVENTIS; US2011/251194; (2011); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts