1-(5-溴吡啶-2-基)环丙烷羧酸甲酯的合成

Synthesis of 1-(5-Bromopyridine-2-yl)Cyclopropane Methyl Formate

以2-(5-溴-2-吡啶)乙腈和1,2-二溴乙烷为原料,二甲基亚砜为溶剂,经过烷基化反应获得1-(5-溴吡啶-2-基)环丙烷-1-腈(3),水解反应生成1-(5-溴吡啶-2-基)环丙烷羧酸(2),酯化反应生成1-(5-溴吡啶-2-基)环丙烷羧酸甲酯(1)。优化反应条件为:投料比n(1,2-二溴乙烷)∶n(2-(5-溴-2-吡啶)乙腈)=1.02∶1.00,n(氢氧化钾)∶n(3)=3.0∶1.0,溶剂二甲基亚砜用量1.8 L,双氧水滴加时间2.0 h,结晶温度-15℃,pH为8.0。优化条件下目标化合物1收率69.5%,纯度98.6%(HPLC)。目标化合物的结构经熔点和1H NMR表征确证。

Using 2-(5-bromo-2-pyridine)acetonitrile and 1,2-dibromoethane as raw materials and dimethyl sulfoxide as solvent,1-(5-bromo-2-pyridinyl)cyclopropane-1-carbonitrile(3)was obtained through alkylation,1-(5-bromo-2-pyridinyl)cyclopropanecarboxylic acid(2)was formed through hydrolysis,and 1-(5-bromo-2-pyridinyl)cyclopropanecarboxylic acid(methyl 1-(5-bromo-2-pyridinyl)cyclopropanecarboxylate(methyl 1-(5-bromopyridinyl)cyclopropanecarboxylate)was obtained through esterification.The reaction conditions for the chemistry were as follows:n(1,2-dibromoethane)∶n(2-(5-bromo-2-pyridine)acetonitrile)=1.02∶1.00,n(potassium hydroxide)∶n(3)=3.0∶1.0,solvent dimethylsulfoxide dosage of 1.8 L,peroxide dropping time of 2.0 h,crystallization temperature of-15℃,and pH 8.0.The yield of target compound 1 under optimised conditions was 69.5%and purity 98.6%(HPLC).The structure of the target compound was confirmed by melting point and 1 H NMR characterisation.