A new synthetic route of 903522-29-2

At the same time, in my other blogs, there are other synthetic methods of this type of compound,903522-29-2, 3,5-Difluoroisonicotinic acid, and friends who are interested can also refer to it.

With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.903522-29-2, name is 3,5-Difluoroisonicotinic acid, molecular formula is C6H3F2NO2, molecular weight is 159.09, as common compound, the synthetic route is as follows.COA of Formula: C6H3F2NO2

Synthesis of 3-Butyl-5-fluoro-isonicotinic acid [A067] 3,5-Difluoro-isonicotinic acid (0.557 g, 3.5 mmol) was suspended in anhydrous THF (8 mL) at 0C, under an atmosphere of nitrogen. To this was added butyl magnesium chloride (2.0 M in diethyl ether, 5.25 mL, 10.5 mmol) dropwise over 10 minutes. The suspension slowly changed form during the slow addition with preliminary agglomeration of solid then the solid started to dissolve slowly, achieving full solution around completion of addition of reagent. The reaction mixture was allowed to warm to room temperature and stirred over 72 hours to form a thick yellow suspension. Diluted with water and transferred into a single neck flask and concentrated in vacuo. The yellow solid was diluted with water (10 mL) and EtOAc (10 mL). The pH was adjusted pH~2, by dropwise addition of HC1 (cone.) and extracted with EtOAc (x3 – some of the yellow colour goes into organics). Combined organics were washed with brine (xl), dried (MgSC^) and concentrated in vacuo to yield the title compound [A067] as an orange gum/solid (0.402g) that solidifies slowly: NMR: (1H, 300MHz, d6-dmso); 8.52 (1H, s), 8.42 (1H, s), 2.67 (2H, t), 1.58-1.48 (2H, m), 1.35-1.22 (2H, m), 0.87 (3H, t); LCMS method: 1, RT: 1.22 min, MI 198 [M+H].

At the same time, in my other blogs, there are other synthetic methods of this type of compound,903522-29-2, 3,5-Difluoroisonicotinic acid, and friends who are interested can also refer to it.

Reference:
Patent; CEPHALON, INC.; CANCER RESEARCH TECHNOLOGY LIMITED; BRESLIN, Henry, J.; DORSEY, Bruce, D.; DUGAN, Benjamin, J.; FOWLER, Katherine, M.; HUDKINS, Robert, L.; MESAROS, Eugen, F.; MONCK, Nathaniel, JT; MORRIS, Emma, L.; OLOWOYE, Ikeoluwa; OTT, Gregory, R.; PAVE, Gregoire, A.; ROFFEY, Jonathan, R. A.; SOUDY, Christelle, N.; TAO, Ming; ZIFICSAK, Craig, A.; ZULLI, Allison, L.; WO2014/52699; (2014); A1;,
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