Synthetic Route of 82668-50-6, 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. 82668-50-6, name is Ethyl 2-(3-Pyrazolyl)acetate belongs to pyrazoles-derivatives compound, it is a common compound, a new synthetic route is introduced below.
Ethyl 2-(1H-pyrazol-3-yl)acetate (180 mg, 1.17 mmol), caesium carbonate (762 mg, 2.34 mmol) and N,N-dimethylformamide (2 mL) were added in a 25 mL single-neck flask. After cooling in an ice bath, methyl iodide (332 mg, 2.34 mmol) was added dropwise, and the reaction was continued for 2 hours in an ice bath. After completion of the reaction monitored by TLC, water (20 mL) was added. Then mixture was extracted with ethyl acetate (3?10 mL), and the organic layers were combined and dried over anhydrous sodium sulfate. Solvent was removed in vacuo to afford a mixture of ethyl 2-(1-methyl-1H-pyrazol-3-yl)acetate and ethyl 2-(1-methyl-1H-pyrazol-5-yl)acetate (yellow oil, 136 mg). Step 5: 2-(1-Methyl-1H-pyrazol-5-yl)acetic acid and 2-(1-methyl-1H-pyrazol-3-yl)acetic acid (0079) The mixture of ethyl 2-(1-methyl-1H-pyrazol-3-yl)acetate and ethyl 2-(1-methyl-1H-pyrazol-5-yl)acetate (136 mg, 0.81 mmol), lithium hydroxide monohydrate (102 mg, 2.43 mmol) and ethanol/H2O (2 mL/0.5 mL) were added in a 25 mL single-neck flask, and the mixture was reacted at room temperature for 0.5 hour. After completion of the reaction, ethanol was removed under reduced pressure, then water (2 mL) was added. The mixture was adjusted to pH 3 with 1N hydrochloric acid and extracted with ethyl acetate (3 10 mL). The organic layers were combined, dried over anhydrous sodium sulfate, and concentrated in vacuo to remove the solvent to give a product (yellow oil, 100 mg). Step 6: Synthesis of N-(2,6-dichloro-3′-cyano-4′-isobutyl-[1,1′-biphenyl]-4-yl)-2-(1-methyl-1H-pyrazol-3-yl)acetami de (9A) and N-(2,6-dichloro-3′-cyano-4′-isobutyl-[1,1′-biphenyl]-4-yl)-2-(1-methyl-1H-pyrazol-5-yl)acetami de (9B) (0080) 4′-Amino-2′,6′-dichloro-4-isobutyl-[1,1′-biphenyl]-3-carbonitrile (40 mg, 0.13 mmol), the mixture of 2-(1-methyl-1H-pyrazol-5-yl)acetic acid and 2-(1-methyl-1H-pyrazol-3-yl)acetic acid (44 mg, 0.32 mmol), HATU (118 mg, 0.38 mmol), N,N-diisopropylethylamine (50 mg, 0.39 mmol) and dichloromethane (2 mL) were added in a 25 mL single-neck flask, and the mixture was reacted at room temperature for 4 hours. The resulting crude product was separated by preparative thin layer chromatography (petroleum ether: ethyl acetate = 1:1) to give N-(2,6-dichloro-3′-cyano-4′-isobutyl-[1,1′-biphenyl]-4-yl)-2-(1-methyl-1H-pyrazol-3-yl)acetami de (white aolid, 26 mg), 1H NMR (400 MHz, CDCl3) delta 9.23 (s, 1H), 7.66 (s, 2H), 7.47 (s, 1H), 7.33 (t, J = 7.4 Hz, 4H), 6.19 (s, 1H), 3.93 (s, 3H), 3.75 (s, 2H), 2.75 (d, J = 7.3 Hz, 2H), 2.02 – 1.97 (m, 1H), 0.97 (d, J = 6.6 Hz, 6H). MS (ESI) m/z: 441.0 (M+1) and N-(2,6-dichloro-3′-cyano-4′-isobutyl-[1,1′-biphenyl]-4-yl)-2-(1-methyl-1H-pyrazol-5-yl)acetami de (white aolid, 27 mg), 1H NMR (400 MHz, CDCl3) delta 8.26 (s, 1H), 7.63 (s, 2H), 7.47 (d, J = 3.3 Hz, 2H), 7.34 (s, 2H), 6.26 (s, 1H), 3.87 (s, 3H), 3.80 (s, 2H), 2.75 (d, J = 7.3 Hz, 2H), 1.97 – 1.88 (m, 1H), 0.97 (d, J = 6.6 Hz, 6H). MS (ESI) m/z: 440.9 (M+1).
The synthetic route of Ethyl 2-(3-Pyrazolyl)acetate has been constantly updated, and we look forward to future research findings.
Reference:
Patent; Fudan University; WANG, Yonghui; HUANG, Yafei; QIU, Ruomeng; TANG, Ting; (68 pag.)EP3581561; (2019); A1;,
Pyrazole – Wikipedia,
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