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. 33252-28-7, name is 6-Chloronicotinonitrile, the common compound, a new synthetic route is introduced below. Formula: C6H3ClN2
A 185 ml stirred autoclave was charged under argon with PdC12(dppp) (213 mg, 0.36 1 mmol), 6- chloro-nicotinonitrile (10 g, 72.2 mmol), dioxane (50 ml), deionized water (50 ml) and sodium, bicarbonate (15.2 g, 0.18 mol, 2.5 molar equivalents). The reaction vessel was closed, purged three times with carbon monoxide (15 bar) and finally charged with carbon monoxide to 60 bar. The mixture was stirred vigorously at 60C under constant pressure for 22 h; after this time no more carbon monoxide absorption was observed. The reaction mixture was transferred to a5 round-bottomed flask with aid of water and, after having removed the organic volatilecomponents on a rotary evaporator, the reaction mixture was worked-up as reported in Example1. Crystallization afforded 5-cyano-pyridine-2-carboxylic acid (9.55 g) as a white solid with 99.6a% purity by HPLC.Example 5a-h5-Cyano-pyridine-2-carboxylic acid A series of reaction conditions was tested using the same procedure described in Example 4. The results are included in the following table.Ex.PbarTCBase ImolarequivalentsSolvent Ivol/volratio2-Cl,5-CN-Py[a%]3-CN-Py-2-C0211[a % I3-CN-Py[a%]Isol.Yield(%)5a6060Na2CO31.25Water 1Dioxane 10.293.51.6895b6060NaOAc2.5Water 1Acetone 13.683.57.9n.d.5c4060Et3N2.5Water 1 t-BuOH 10.795.91.0895d1560Et3N2.5Water 1t-BuOH 4<0.195.41.992Se70100Et3N2.2Water 1THF40.453.825n.d.Sf3580Et3N2.5Water 1 CH3CN 4<0.193.54.9n.d.Sg3580Et3N2.5Water 1CH3CN 4MeOH 1<0.191.51.5n.d.5h4050Et3N2.5Water 1t-BuOH 110.586.60.5n.d.Example no. Sc: reaction time S h; example no. Sd and Sh: reaction time 16 h; example no. Sf:reaction time 12 h.Examples no. Se and Sf: S g of 2-Cl,S-CN-Py, S/C 330.Example no. Sg: crude mixture contains 3.7 a% of the methyl ester 3-CN-Py-2-CO2Me. a% S values are obtained by HPLC analysis.
The synthetic route of 33252-28-7 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; FETTES, Alec; MARTY, Hans-Peter; SCALONE, Michelangelo; WO2014/173917; (2014); A1;,
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