Month: May 2021

Application of 191014-55-8,Some common heterocyclic compound, 191014-55-8, name is 4-Fluoro-2-methoxybenzonitrile, molecular formula is C8H6FNO, 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 g of 4-fluoro-2-methoxy-benzonitrile in 15 ml_ of dichloroethane was added 1.1 g of aluminium trichloride. The resulting mixture was refluxed for 1 day then poured slowly into water and extracted with ethyl acetate. The organic extracts were washed twice with 10% aqueous solution of sodium hydroxide. The combined basic layers were washed twice with ethyl acetate, acidified with concentrated aqueous solution of hydrochloric acid and extracted three times with ethyl acetate. The combined organic extracts were washed with water, with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give 0.78 g of 4-fluoro-2- hydroxy-benzonitrile as a white solid. C7H4FNO (137.11), MS(ESI): 138.17 (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 4-Fluoro-2-methoxybenzonitrile, its application will become more common.

Reference:
Patent; SANOFI-AVENTIS DEUTSCHLAND GMBH; WO2007/39172; (2007); A1;,
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Application of 53005-44-0, 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. 53005-44-0, name is 2-Methoxy-6-methylbenzonitrile, This compound has unique chemical properties. The synthetic route is as follows.

Intermediate 146 1-(2-methoxy-6-methylphenyl)-2-phenylethanone: To intermediate 145 (5.0 g, 34.03 mmol) in THF (50 ml), benzylmagnesium chloride (34 ml, 2M in THF, 68.02 mmol) was added at 0 C. over 30 min and heated to reflux for 15 h. The reaction mixture was cooled to room temperature, 2N HCl (200 ml) was added and again refluxed for 4 h. The reaction mixture was cooled and extracted with ethyl acetate, dried over sodium sulphate and concentrated. The crude product was column chromatographed with ethyl acetate:petroleum ether to afford to afford the title compound as brown liquid (3.7 g, 45%). 1H-NMR (delta ppm, CDCl3, 400 MHz): 7.30-7.18 (m, 6H), 6.76 (m, 2H), 4.07 (s, 2H), 3.83 (s, 3H), 2.02 (s, 3H).

The chemical industry reduces the impact on the environment during synthesis 2-Methoxy-6-methylbenzonitrile. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Rhizen Pharmaceuticals SA; US2012/289496; (2012); A1;,
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Reference of 10444-38-9, These common heterocyclic compound, 10444-38-9, name is Ethyl 4-cyanobutanoate, 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.

PREPARATION 1 Ethyl 4-(1H-tetrazole-5-yl)butanoate Ethyl 4-cyanobutyrate (approximately 15 g) was dissolved in DME. Tris(n-butyl)tin azide (5 ml) was added and the reaction solution was heated to 85 overnight then cooled to room temperature. The cooled solution was diluted with methanol (20 ml) then 1N hydrochloric acid (20 ml) was added. The solution was stirred for one hour then partitioned between ethyl acetate and water. The organic layer was separated, dried over magnesium sulfate and evaporated under reduced pressure. The residue was chromatographed by preparatory-scale HPLC (silcia column) eluted with a gradient of 30 to 70% ethyl acetate in hexane plus 1% acetic and to yield 3.39 g of the title product: n.m.r.(300 MHz, CDCl3) delta: 4.2 (q, 2H); 2.95 (t, 2H); 2.5 (t, 2H); 2.1 (t, 2H); 1.3 (t, 3H).

The synthetic route of 10444-38-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Eli Lilly and Company; US4820723; (1989); A;,
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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. 6575-10-6, name is 2-Chloro-6-methoxybenzonitrile, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 6575-10-6

To a solution of A5.2 (334 mg, 2.0 mmol) in 10.0 mL THF was added of borane (2.0 mol/L). The mixture was heated at 90 oC for 3 h, then cooled to rt and quenched with methanol. The mixture was concentrated under vacuum, the residue was diluted with another 50 mL methanol, and then removed again. The process was repeated for four times to give the title compound (300 mg, 88%) as the crude product, which will used in next step without further purification. LC-MS: [MH]+ = 172.1

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 6575-10-6.

Reference:
Patent; NOVARTIS AG; CHAN, Ho Man; FU, Xingnian; GU, Xiang-Ju Justin; HUANG, Ying; LI, Ling; MI, Yuan; QI, Wei; SENDZIK, Martin; SUN, Yongfeng; WANG, Long; YU, Zhengtian; ZHANG, Hailong; ZHANG, Ji Yue; ZHANG, Man; ZHANG, Qiong; ZHAO, Kehao; (193 pag.)WO2017/221092; (2017); A1;,
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Electric Literature of 25978-68-1, 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 25978-68-1 as follows.

To a solution of methyl 4-cyano-3-methylbenzoate (36 mg, 0.205 mmol) in 1,4-dioxane (0.5 mL) and water (0.500 mL), was added sodium hydrogen sulfide (0.019 mL, 0.616 mmol) and triethylamine hydrochloride (170 mg, 1.233 mmol). The reaction mixture was heated at 55 0C overnight. The reaction was allowed to cool and water was added. The mixture was extracted with EtOAc. The combined organic layers were dried (Na2SC^), filtered and the solvent was evaporated in vacuo to give the product as a yellow solid. LCMS calc. = 210.1; found = 210.2 (M+l)+. 1H NMR (500 MHz, CDCl3) 7.86 (s, 1 H); 7.84 (d, J = 8.1 Hz, 1 H); 7.42 (d, J= 7.9 Hz, 1 H); 7.16 (s, 2 H); 3.93 (s, 3 H); 2.51 (s, 3 H).

According to the analysis of related databases, 25978-68-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MERCK & CO., INC.; WO2007/79186; (2007); A2;,
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Synthetic Route of 64113-86-6, A common heterocyclic compound, 64113-86-6, name is 5-Methyl-2-nitrobenzonitrile, molecular formula is C8H6N2O2, 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.

5-Methyl-2-nitrobenzonitrile (1.92 g, 11.84 mmol) was added in portions to a stirred solution of SnCl2 (11.22 g, 59.2 mmol) in conc. HCl (12 mL) and EtOH (12 mL). The reaction temperature was maintained at 20-30 C. using an ice bath. The reaction mixture was then stirred at room temperature for 1 h and poured into an ice cold aqueous solution of NaOH (6N, app. 30 mL) to neutralize to pH7. The product was extracted into EtOAc, washed with brine, dried over MgSO4 and concentrated to provide the title product (1.56 g, 99%) as a yellow-brown solid. 1H NMR (400 MHz, DMSO-d6) delta 2.21 (s, 3H), 5.79 (bs, 2H), 6.68-6.71 (d, 1H), 7.10-7.13 (dd, 1H), 7.15 (s, 1H). 13C NMR (DMSO-d6) delta 20.13, 93.99, 116.12, 118.94, 125.38, 132.32, 135.76, 150.21. MS 133 (MH+).

The synthetic route of 64113-86-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SENOMYX, INC.; US2008/306053; (2008); A1;,
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Electric Literature of 17354-04-0, 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 17354-04-0 as follows.

General procedure: Piperidine (0.03 ml, 5 mol %) was added to a warm solution of the appropriate salicylaldehyde 5 (5 mmol) and 2-(4,5-dimethoxy-2-nitrophenyl)acetonitrile (1.12 g, 5 mmol) in EtOH (10 ml). The resulting solution was refluxed with stirring for 5 h. The mixture was treated with a solution of concentrated H2SO4 (0.55 ml) in EtOH (2 ml) and refluxed with stirring for 2 h. The obtained precipitate was filtered, washed with EtOH (10 ml), hot H2O (40 ml) and finally with EtOH (10 ml), and dried at 100 C.

According to the analysis of related databases, 17354-04-0, the application of this compound in the production field has become more and more popular.

Reference:
Article; Irgashev, Roman A.; Karmatsky, Arseny A.; Slepukhin, Pavel A.; Rusinov, Gennady L.; Charushin, Valery N.; Tetrahedron Letters; vol. 54; 42; (2013); p. 5734 – 5738;,
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Some common heterocyclic compound, 86770-80-1, name is 3,3-Difluorocyclobutanecarbonitrile, molecular formula is C5H5F2N, 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. Product Details of 86770-80-1

A solution of 3,3-difluorocyclobutane-l-carbonitrile (1 g, 8.54 mmol) in ethanol (15 mL) was treated with hydroxylamine (50% in water) (5.25 mL, 86.0 mmol) and stirred at 80 C for 3 h. The reaction mixture was allowed to cool and then concentrated in vacuo. The residue was partitioned between DCM (10 mL) and water (10 mL). The organic phase was separated, the aqueous phase was extracted with DCM (3 x 5 mL),. The product re-extracted with 1 : 1 IPA/CHCI3 (3 x 60 mL), organic separated and dried over sodium sulfate and concentrated in vacuo to afford the title compound as an orange gum (545 mg,42%). 1H NMR (500 MHz, DMSO-d6) delta 9.07 (s, 1H), 5.44 (s, 2H), 2.84 – 2.59 (m, 5H). LCMS (ES+) RT 0.25 min, 151.0 (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 86770-80-1, its application will become more common.

Reference:
Patent; UCB BIOPHARMA SPRL; ALEXANDER, Rikki, Peter; BRACE, Gareth, Neil; BROWN, Julien, Alistair; CALMIANO, Mark, Daniel; CHOVATIA, Praful, Tulshi; DELIGNY, Michael; GALLIMORE, Ellen, Olivia; HEER, Jag, Paul; JACKSON, Victoria, Elizabeth; KROEPLIEN, Boris; MAC COSS, Malcolm; QUINCEY, Joanna, Rachel; SABNIS, Yogesh, Anil; SWINNEN, Dominique, Louis, Leon; ZHU, Zhaoning; WO2015/86526; (2015); A1;,
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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 138642-47-4 as follows. HPLC of Formula: C8H6BrNO

Step A: 1-(2-Bromo-5-methoxyphenyl)methanamine 2-Bromo-5-methoxybenzonitrile (10.0 g, 47.2 mmol) was dissolved in dry tetrahydrofuran (100 mL) in a flame-dried flask and cooled in an ice bath. A solution of borane in tetrahydrofuran (75 mL, 75 mmol, 1.0 M) was added dropwise over a period of 30 minutes. The reaction mixture was stirred overnight at rt, then quenched slowly with ice water and Na2CO3 (saturated aqueous solution). After removal of THF, the residue was extracted with large amounts of EtOAc three times. The combined organic layers were washed with water, dried, and concentrated to give the crude, which was purified by silica gel column chromatography to give the desired product as a white powder (3.65 g, 36%). LCMS for C8H10BrNO (M+H)+: m/z=216.9, 219.0.

According to the analysis of related databases, 138642-47-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; INCYTE CORPORATION; US2010/190804; (2010); A1;,
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Synthetic Route of 38469-84-0,Some common heterocyclic compound, 38469-84-0, name is 5-Methoxy-2-nitrobenzonitrile, molecular formula is C8H6N2O3, 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.

2-Amino-5-methoxybenzonitrile: [0441] A 100 mL round bottom flask was charged with 5-methoxy-2- nitrobenzonitrile (1.7 g, 9.55 mmol), sodium dithionite (4.99 g, 29 mmol), water (15 mL) and EtOH (50 mL). The resulting mixture was heated at reflux for 1 h. Work-up: the reaction mixture was concentrated in vacuo to remove ethanol then extracted with EtOAc (50 mL). The organic layer was dried over anhydrous Na2S04 and concentrated in vacuo, to afford 1.4 g (quantitative) of the product as yellow oil. It was used in the next step without further purification.

The synthetic route of 38469-84-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; KALYPSYS, INC.; BORCHARDT, Allen; DAVIS, Robert; BEAUREGARD, Clay; BECKER, Daniel; GAMACHE, Daniel; NOBLE, Stewart, A.; HELLBERG, Mark, R.; KLIMKO, Peter, G.; ZHIHAI, Qui; PAYNE, Joseph, E.; YANNI, John; WO2011/112731; (2011); A2;,
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