Analyzing the synthesis route of Ethyl 2-chloronicotinate

According to the analysis of related databases, 1452-94-4, the application of this compound in the production field has become more and more popular.

Electric Literature of 1452-94-4, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 1452-94-4, name is Ethyl 2-chloronicotinate, molecular formula is C8H8ClNO2, The compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

In a 500 mL dry round bottom flask with reflux condenser and magnetic stirrer was placed with 2-chloro-3-ethyl nicotinate (40.0 g, 215.5 mmol) in methanol (200 mL). CH3ONa in methanol (25%, 65 mL, 301.7 mmol) was added slowly and the reaction mixture was refluxed for 16 h. The reaction was cooled to rt, quenched by addition of a saturated aqueous NH4Cl solution. The aqueous mixture was extracted with ethyl acetate. The combined organic layers were washed well with water, brine, dried over Na2SO4 and concentrated to give 35 g of 2-methoxy-3-methyl nicotinate with 97% yield. Sodium hydride (60% in oil, 9.21 g, 230.3 mmol) was added to a dry 500 mL round bottom flask followed by 100 mL DMF. 4-Methoxyacetophenone (31.45 g, 209.44 mmol) in 50 mL dry DMF was added dropwise at 0 C. over 30 min. The reaction mixture was stirred for 1 h at rt. 2-Methoxynicotinic acid methyl ester (35 g, 209.44 mmol) was dissolved in 50 mL dry DMF and added slowly, keeping the temperature at 0 C. The mixture was stirred for 16 h at rt, then quenched by addition of a saturated aqueous NH4Cl solution and diluted with water. The solid was filtered off, washed with water and dried to give 56.7 g diketo product in 95% yield.

According to the analysis of related databases, 1452-94-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; RVX Therapeutics Inc.; McLure, Kevin G.; Young, Peter R.; US2013/281396; (2013); A1;,
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