Author: Jessica.F

Synthetic Route of 64248-63-1, The chemical industry reduces the impact on the environment during synthesis 64248-63-1, name is 3,5-Difluorobenzonitrile, I believe this compound will play a more active role in future production and life.

3-Fluoro-5-methoxybenzoic Acid In a 250 ml round bottom flask equipped with stir bar added 3,5-Difluorobenzonitrile (4.2 g, 30.4 mmol), sodium methoxide (10.4 ml, 45.6 mmol, 25% methanol) and dimethylformamide (40 ml). Stirred the resulting reaction mixture at room temperature, overnight. The reaction mixture was concentrated in-vacuo and residue was dissolved in dichloromethane (200 ml). The organic phase was washed sequentially with water (150 ml) and brine (150 ml), dried (sodium sulfate) and concentrated in-vacuo. The crude residue was purified on silica gel using 10% diethyl ether in hexanes to isolate 3-Fluoro-5-methoxybenzonitrile (1.63 g) as a white 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, 3,5-Difluorobenzonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Wagenen, Bradford Van; Stormann, Thomas M.; Moe, Scott T.; Sheehan, Susan M.; McLeod, Donald A.; Smith, Daryl L.; Isaac, Methvin Benjamin; Slassi, Abdelmalik; US2003/55085; (2003); A1;,
Nitrile – Wikipedia,
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Adding a certain compound to certain chemical reactions, such as: 134997-74-3, name is 3-Oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbonitrile, 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 134997-74-3, Quality Control of 3-Oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbonitrile

To a stirred solution of 3-oxo-3,4-dihydro-2H-benzo[b][1 ,4]oxazine-6-carbonitrile (3.30 g, 1 9.0 mmol) in N,N-dimethylformamide (35 mL) was added sodium hydride (758 mg, 1 9 mmol, 60% dispersion in mineral oil) and iodoethane (3.84 g, 25 mmol, 1 .97 mL) at 0 C. The mixture was warmed to 20 00. After 3 h, the mixture was cooled to 0 C, quenched by addition of water (50 mL), and extracted with ethylacetate (60 mL x 4). The combined organic phases were washed with saturated aqueous sodium chloride solution (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to give crude product that was purified by chromatography (silica, petroleum ether : ethyl acetate 50:1 to 5:1) to give 4-ethyl-3-oxo-3,4-dihydro-2H-benzo[b][1 ,4]oxazine-6-carbonitrile (1 .30 g, 6.43 mmol, 34 %) as a white solid. 1H NMR (400 MHz, CDC3) O 7.25 (dd, J 1.8, 8.3 Hz, 1 H), 7.17 (d, J 1 .8 Hz, 1 H), 6.98 (d, J8.3 Hz, 1H), 4.62 (s, 2H), 3.93 (q, J 7.2 Hz, 2H), 1.23 (t, J 7.2 Hz, 3H); LOMS (ESI) m/z 203.1 [M÷H]÷.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbonitrile, and friends who are interested can also refer to it.

Reference:
Patent; YUMANITY THERAPEUTICS; LUCAS, Matthew; LE BOURDONNEC, Bertrand; WRONA, Iwona; PANDYA, Bhaumik; TIVITMAHAISOON, Parcharee; OZBOYA, Kerem; VINCENT, Benjamin; TARDIFF, Daniel; PIOTROWSKI, Jeff; SOLIS, Eric; SCANNEVIN, Robert; CHUNG, Chee-Yeun; ARON, Rebecca; RHODES, Kenneth; (489 pag.)WO2018/81167; (2018); A1;,
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Adding a certain compound to certain chemical reactions, such as: 16588-02-6, name is 2-Chloro-5-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 16588-02-6, Recommanded Product: 16588-02-6

A mixture of 3 -methyl- IH-1, 2;4-triazole (6.83 g, 82 mmol), 2- chloro-5-mtrobenzomtrile (15 g, 82 mmol), and potassium carbonate (34.1 g, 246 mmol) in anhydrous acetonitrile (200 mL) was heated at 70 0C for 16 h. The dark brown reaction mixture was allowed to cool to rt and was poured into water (500 mL). The aqueous mixture was extracted with EtOAc (3 x 200 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified using silica gel chromatography (40-100% ethyl acetate/hexane, linear gradient) to afford 2-(3-methyl~lH-l,2,4-triazol-l-yl)-5- nitrobenzonitrile (10.9 g, 58 % yield). LC-MS (M+H)+ – 230.1. 1H NMR (500 MHz, chloroform-D) delta ppm 2.53 (s, 3 H) 8.10 (d, J-9.16 Hz, 1 H) 8.56 (dd, J-9.16, 2.44 Hz, 1 H) 8.68 (d, J-2.44 Hz, 1 H) 8.93 (s, 1 H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Chloro-5-nitrobenzonitrile, and friends who are interested can also refer to it.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; MARCIN, Lawrence, R.; THOMPSON, Lorin, A., III; BOY, Kenneth, M.; GUERNON, Jason, M.; HIGGINS, Mendi, A.; SHI, Jianliang; WU, Yong-Jin; ZHANG, Yunhui; MACOR, John, E.; WO2010/83141; (2010); A1;,
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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. 6609-57-0, name is 2-Ethoxybenzonitrile, This compound has unique chemical properties. The synthetic route is as follows., Application In Synthesis of 2-Ethoxybenzonitrile

Preparation 7 2-ethoxy-5-(4-ethyl-1-piperazinylsulfonyl)benzonitrile Commercially available 2-ethoxybenzonitrile (25 g, 0.17 Mol) was added dropwise to an ice cooled mixture of chlorosulfonic acid (50.8 mL, 0.765 Mol) and thionyl chloride (12.4 mL, 0.17 Mol) so as to keep the temperature below 10 C. The reaction was then stirred at ambient temperature for 18 h before being poured onto ice/water. This mixture was stirred 1 hr before the precipitated material was filtered off. The resultant solid was dissolved in acetone (300 mL) and triethylamine (25 mL, 0.179 Mol) was added followed by a slow addition of N-ethylpiperazine (25 mL, 0.198 Mol).

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 6609-57-0.

Reference:
Patent; Dunn, Peter James; Dunne, Catherine; US2002/13464; (2002); A1;,
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Some common heterocyclic compound, 4475-95-0, name is 2-Amino-2-methylbutanenitrile, molecular formula is C5H10N2, 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: nitriles-buliding-blocks

5.00 g (50.94 mmol) of 2-amino-2-methylbutanonitrile [synthesis described in: Lonza AG, U.S. Pat. No. 5,698,704 (1997); Deng, S. L. et al. Synthesis 2001, 2445; Hjorringgaard, C. U. et al. J. Org. Chem. 2009, 74, 1329; Ogrel, A. et al. Eur. J Org. Chem. 2000, 857] were initially charged in 50 ml of THF and 6.5 ml of water, 21.83 g (157.92 mmol) of potassium carbonate were added and, at 0 C., 7.9 ml (56.04 mmol) of benzyl chlorocarbonate (benzyl chloroformate) were added. After the addition of 8 ml of THF and 3 ml of water, the reaction mixture was stirred overnight, slowly warming to RT. Water was then added, and the mixture was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated. The residue was dissolved in diethyl ether and precipitated with petroleum ether. The product was filtered off and the solid was washed with a little petroleum ether and dried under high vacuum. This gave 11.35 g of the target compound (93% of theory, purity 97%). LC-MS (Method 5): Rt=0.97 min MS (ESpos): m/z=233 (M+H)+1H NMR (400 MHz, DMSO-d6): delta=0.95 (t, 3H), 1.51 (s, 3H), 1.75-1.95 (m, 2H), 5.07 (s, 2H), 7.30-7.43 (m, 4H), 7.88-8.03 (m, 1H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4475-95-0, its application will become more common.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; VAKALOPOULOS, Alexandros; VALOT, Gaelle; LINDNER, Niels; FOLLMANN, Markus; STASCH, Johannes-Peter; WUNDER, Frank; MARQUARDT, Tobias; DIETZ, Lisa; LI, Volkhart Min-Jian; (74 pag.)US2017/233345; (2017); A1;,
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51762-67-5, name is 3-Nitrophthalonitrile, 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. category: nitriles-buliding-blocks

4-(methylthio)phenol (0.809 g, 5.78 mmol) was dissolved in10 cm3 dry DMF and thenfinely dried K2CO3 (~2.00 g, excess) wasadded to this mixture. Then 3-nitrophthalonitrile (1.00 g,5.78 mmol) was added to this mixture dropwise by stirringeffectively at 40 C under the N2 atmosphere. The reaction mixturewas kept for 3 day at this temperature under N2 atmosphere. Afterthe reaction mixture was cooled to room temperature, it waspoured into ca. 200 cm3 ice-water media. The occured precipitatewasfiltered and then washed with ca. 100 cm3 water up to thewashings became neutral. The occured precipitate wasfiltered anddissolved in CHCl3 and washed with%5 NaHCO3 to eliminate thebeginning residual compounds. The creamy solution was thentreated with anhydrous Na2SO4 until become dry andfiltered. Itwas purified by chromatography over a silica gel column by using aeluent that is a mix of CHCl3: MeOH (100/5), giving white powder,(1). Finally, the pure powder was dried in a vacuo. Yield of (1): 1.28 g (83%); m.p. = 119 C; Anal. Calcd forC15H10N2OS (266 g mol1C, 67.65; H, 3.78; N, 10.52 Found: C,67.58; H, 3.52; N, 10.30. FT-IR (cm1); 3068 (w, Ar-CH), 2922 (w,Alip-CH), 2228 (CRN, st), 1610(CC), 1567 (CN), 1484(st), 1273(Ar-S-Alip-CH), 1088, 1009, 985, 847, 795. 1H NMR (DMSO-d6) delta:8.11 (t, 1H, meta to Ar-O-Ar and CN), 7.88 (d, 1H, ortho to Ar-O-Ar),7.52 (d,1H, ortho to CN), 7,367.01 (m, 4H, O-Ar-S) 2.23(s, 3H, CH3-S-Ar). 13C NMR (DMSO-d6) delta: 165.4, 156.7, 141.4, 141.1, 133.5, 133.4,127.1, 126.3, 121.2, 121.1, 118.8, 110.2, 20.4. EI/MS m/z: 266.12 [M]+.

The synthetic route of 51762-67-5 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Guensel, Arma?an; Guezel, Emre; Bilgicli, Ahmet T.; ?i?man, ?lkay; Yarasir, M. Niluefer; Journal of Photochemistry and Photobiology A: Chemistry; vol. 348; (2017); p. 57 – 67;,
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21524-39-0, name is 2,3-Difluorobenzonitrile, 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. Formula: C7H3F2N

Potassium nitrate (404 mg, 4.0 mmol) to a solution of 2,3- difluorobenzonitrile (278 mg, 2.0 mmol) in sulfuric acid (2 mL) at 00C. After stirring at 00C for 2 h the reaction was quenched with ice water (5 mL). The mixture was extracted with ethyl acetate (3×10 mL). The organic layer was dried and concentrated to give the crude product which was purified by silica gel (PE : EA = 40 : 1) to give the title compound as a yellow solid. (40 mg, 11%). 1H NMR (400 MHz, CDCl3): delta 8. 25-8.22 (m, IH), 7.69-7.63 (m, IH). LC/MS: m/e = 185 (M+H)+.

The synthetic route of 21524-39-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SEPRACOR INC.; BURDI, Douglas; SPEAR, Kerry, L.; HARDY, Larry, Wendell; WO2010/114971; (2010); A1;,
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Electric Literature of 149793-69-1, These common heterocyclic compound, 149793-69-1, name is 3-Fluoro-5-(trifluoromethyl)benzonitrile, 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: General procedure for nucleophilic substitution: A solution of 3-fluoro-5-trifluoromethyl-benzonitrile (1 eq) and the corresponding amine (3eq) in DMA was stirred at 145C during 3h. NaCl(aq) was added. The product was taken off into ethyl acetate. The organic layer was washed two times with water then dried over Na2S04 and evaporated under reduced pressure to give the intermediate compounds.

The synthetic route of 149793-69-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ORIBASE PHARMA; CHEVE, Gwenael; DAYDE-CAZALS, Benedicte; FAUVEL, Benedicte; BORIES, Cedric; YASRI, Abdelaziz; WO2014/102377; (2014); A1;,
Nitrile – Wikipedia,
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Reference of 6136-93-2, 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 6136-93-2 as follows.

(iii) 2.2-Diethoxyethanethioamide(See, for example, Inami, K., Shiba, T., Bull. Chem. Soc. Jpn., 1985, 58, 352.) Diethoxyacetonitrile (0.050 g, 0.5 mmol; see step (ii) above) was placed in a 10 mL microwavable vial, methanol (5 mL) and (NEU)2S (54 muL, 0.5 mmol (40% wt solution in water)) was then added. The vial was then heated to 8O0C at IOOW for 15 min and the reaction then allowed to cool to RT. The solvent was then removed under reduced pressure and the residue dissolved in ethyl acetate (15 mL) and extracted with water (2 x 10 mL) and brine (2 x 5 mL). The organic layer was then dried (MgSO4), filtered and concentrated under reduced pressure to yield the sub-title compound as a white/off- white solid (0.081 g, 99%). m.p. = 92-94C. V1113x KBr/cm”1: 3335, 3171 upsilon(N-H), 2976, 2885 upsilon(C-H), 2247 upsilon(N?C), 1645, 1449 upsilon(C=S), 1019 delta(C-O). deltaH 1H(CDCl3): 1.26 (6H5 1, 2(CH3) (J=8.0Hz)), 3.71 (4H, m, 2(CH2)), 5.05 (IH, s, C-H), 7.70 (2H, d, N-H).

According to the analysis of related databases, 6136-93-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; UNIVERSITY OF STRATHCLYDE; WO2008/38018; (2008); A1;,
Nitrile – Wikipedia,
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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;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts