Category: 500912-18-5

Synthetic Route of 500912-18-5, A common heterocyclic compound, 500912-18-5, name is 2-(2-Fluoro-6-methoxyphenyl)acetonitrile, molecular formula is C9H8FNO, 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.

First, sodium bis(trimethylsilyl) amide (1.0 M tetrahydrofuran solution) (1.6 mL) was added dropwise to a solution of 2-(2-fluoro-6-methoxyphenyl)acetonitrile (86 mg) in tetrahydrofuran (2.4 mL) under ice cooling, and the mixture was stirred at the same temperature for 30 minutes. N-benzyl-bis(2-chloroethyl)amine hydrochloride (140 mg) was added to the resultant solution, followed by reflux for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and then was dried with anhydrous magnesium sulfate. the solvent was removed by evaporation under reduced pressure. The obtained residue was purified by silica gel column chromatography (diethylether/n-hexane = 50/50) to obtain 1-benzyl-4-(2-fluoro-6-methoxyphenyl)piperidine-4-carbonitr ile (132 mg). 1H-NMR (400MHz, CDCl3) delta: 2.28-2.37(m,2H),2.43-2.50(m,2H),2.50-2.59(m,2H),2.89-2.98(m ,2H),3.58(s,2H),3.91(s,3H),6.67(ddd,J=12.9,8.4,1.2Hz,1H),6. 74(d,J=8.3Hz,1H),7.21-7.29(m,3H),7.29-7.36(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; RIKEN; Japanese Foundation For Cancer Research; YOSHIDA, Minoru; SEIMIYA, Hiroyuki; OKUE, Masayuki; YASHIRODA, Yoko; SHIRAI, Fumiyuki; TSUMURA, Takeshi; KANO, Yuko; WASHIZUKA, Kenichi; YOSHIMOTO, Nobuko; KOUDA, Yasuko; FUKAMI, Takehiro; CHIKADA, Tsubasa; WATANABE, Takashi; (261 pag.)EP3480198; (2019); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Adding a certain compound to certain chemical reactions, such as: 500912-18-5, name is 2-(2-Fluoro-6-methoxyphenyl)acetonitrile, 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 500912-18-5, name: 2-(2-Fluoro-6-methoxyphenyl)acetonitrile

[0428] Under argon and at -78C., a mixture of 2.5 M butyllithium solution in hexane (13 ml, 33 mmol) and THF (50 ml) was added slowly to a solution of N,N-diisopropylethylamine (5.8 ml, 33 mmol) in THF (75 ml). The reaction mixture was allowed to warm to 0C., stirred at 0C. for 5 min and cooled back down again to -78C. A solution of (2-fluoro-6-methoxyphenyl)acetonitrile (5.00 g, 30.3 mmol, CAS-RN 500912-18-5, commercially available) in THF (25 ml) was then added slowly. The reaction mixture was once more allowed to warm to 0C., stirred at 0C. for 5 min and cooled back down again to -78C. A solution of iodomethane (2.0 ml, 31.79 mmol) in THF (25 ml) was then added slowly. The mixture was stirred overnight, with the temperature gradually rising to RT. At 0C., saturated ammonium chloride solution and water (50 ml each) were then added and the mixture was shaken and extracted twice with ethyl acetate (150 ml each). The combined organic phases were washed once with saturated aqueous sodium chloride solution (200 ml), dried over sodium sulfate, filtered and concentrated, and the residue was taken up in dichloromethane and purified by flash column chromatography (400 g of silica gel Buchi Snap-Cartridge KP-Sil, cyclohexane/ ethyl acetate 9:1). The combined target fractions were concentrated, and the residue was (briefly) dried under reduced pressure. This gave 3.33 g (100% purity, 61% of theory) of the title compound. [0429] GC-MS (Method 12): Rt=4.31 min; MS (ESIpos): m/z=179 [M]+ [0430] 1H-NMR (400 MHz, DMSO-d6) delta [ppm]: 1.492 (15.85), 1.509 (16.00), 3.314 (9.13), 3.887 (0.90), 4.452 (0.69), 4.455 (0.70), 4.470 (2.12), 4.473 (2.10), 4.488 (2.11), 4.491 (2.05), 4.505 (0.69), 4.508 (0.65), 6.861 (1.62), 6.863 (1.60), 6.884 (2.45), 6.907 (1.81), 6.909 (1.81), 6.943 (3.36), 6.964 (3.72), 7.353 (1.56), 7.370 (1.87), 7.374 (2.99), 7.391 (3.02), 7.395 (1.60), 7.412 (1.36). [0431] 1H-NMR (400 MHz, DMSO-d6): 5 [ppm]=7.44-7.30 (m, 1H), 6.95 (d, 1H), 6.92-6.85 (m, 1H), 4.48 (qd, 1H), 3.88 (s, 3H), 1.50 (d,3H).

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-(2-Fluoro-6-methoxyphenyl)acetonitrile, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Bayer Aktiengesellschaft; Bayer Pharma Aktiengeseiisehaft; BECK, Hartmut; KAST, Raimund; MEININGHAUS, Mark; DIETZ, Lisa; FUERSTNER, Chantal; STELLFELD, Timo; ANLAUF, Sonja; VON BUEHLER, Clemens-Jeremias; BAIRLEIN, Michaela; ANLAHR, Johanna; MUENSTER, Uwe; TERJUNG, Carsten; JOERISSEN, Hannah; HAUFF, Peter; MUELLER, Joerg; DROEBNER, Karoline; NAGEL, Jens; (220 pag.)US2020/31775; (2020); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Reference of 500912-18-5, 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 500912-18-5 as follows.

A mixture of 6-chloro-4-(ethyl amino) nicotinaldehyde (Scheme 1 compound 6) (1.7 g, 9.32 mmol), Scheme 56 compound 4 (2.0 g, 12.11 mmol) and K2C03 (3.8 g, 27.96 mmol) in dry DMF (10 mL) was heated to 100 C under nitrogen atmosphere for 16 h. After TLC showed the starting material was completely consumed, the reaction mixture was cooled to RT, diluted with EtOAc (2 x 50 mL), washed with water (2 x 20 mL) and brine (10 mL) then dried over Na2S04 and concentrated to give a residue which was purified by flash chromatography on silica gel (eluting with petroleum ether/EtOAc 100/0 gradually increasing to 60/40) to give 7-chloro-l-ethyl-3-(2-fluoro-6-methoxyphenyl)-l,6-naphthyridin-2(lH)- imine (800 mg, 26%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6): delta 8.41 (s, 1H), 7.51 (q, J= 8.0 Hz, 1H), 7.41 (d, J= 10.6 Hz, 2H), 7.07-6.92 (m, 2H), 4.26 (m, 2H), 3.77 (d, J = 2.4 Hz, 3H), 1.22-1.16 (m, 3H). MS [ESI, MH+] = 332.09.

According to the analysis of related databases, 500912-18-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MANNKIND CORPORATION; TOLERO PHARMACEUTICALS, INC.; ZENG, Qingping; FARIS, Mary; MOLLARD, Alexis; WARNER, Steven L.; FLYNN, Gary A.; WO2014/52365; (2014); A1;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts