New downstream synthetic route of Methyl 3-chloroisonicotinate

At the same time, in my other blogs, there are other synthetic methods of this type of compound,98273-79-1, Methyl 3-chloroisonicotinate, 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.98273-79-1, name is Methyl 3-chloroisonicotinate, molecular formula is C7H6ClNO2, molecular weight is 171.58, as common compound, the synthetic route is as follows.Quality Control of Methyl 3-chloroisonicotinate

A solution of 1-(bromomethyl)-4-(methylsulfanyl)benzene (prepared according to D. D. M. Wayner, D. R. Arnold, Can J. Chem., 1984, 62, 1164) (2.54 g, 11.7 mmol) in THF (10 mL) was added dropwise to a slurry of Riecke Zinc in THF (22.8 mL of a commercial suspension [5g Zn/100 mL], 17.5 mmol) under nitrogen. During this time the temperature rose steadily to 35C. After allowing the black slurry to cool to room temperature over 30 min bis(triphenylphosphine)nickel (II) chloride (762 mg, 1.17 mmol) was added followed by a solution of methyl 3-chloroisonicotinate (prepared according to J. Epsztajn, M. W. Plotka, A. Grabowska, Synth. Commun., 1997, 27, 1075) (1.0 g, 5.83 mmol) in THF (10 mL), dropwise, taking care to keep the temperature below 30C. After the addition was complete the reaction was allowed to cool to room temperature over 1 h before being quenched by the addition of sat. NH4Cl (aq) (20 mL) while cooling with an ice bath. The mixture was filtered through Celite ), washing well with EtOAc (3 x 20 mL), the organic layer was separated, dried (MgS04) and evaporated to give a brown oil. The residue was purified by column chromatography [SiO2; EtOAc:pentane, 1:3 increasing polarity to EtOAc:pentane, 1:1 and then to (EtOAc:MeOH:NH40H, 95:5:0.5):pentane, 1:1] to give the title compound as an orange oil; & delta H (CDCl3, 400 MHz) 2.43 (3H, s), 3.82 (3H, s), 4.30 (2H, s), 7.05 (2H, d), 7.18 (2H, d), 7.67 (1H, br), 8.59 (2H, br); MS m/z (TS+) 274 (MH+)

At the same time, in my other blogs, there are other synthetic methods of this type of compound,98273-79-1, Methyl 3-chloroisonicotinate, and friends who are interested can also refer to it.

Reference:
Patent; Pfizer Limited; Pfizer Inc.; WO2004/16593; (2004); A1;,
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