医药中间体甲氧胺盐酸盐的绿色合成工艺

STUDY ON GREEN SYNTHESIS TECHNOLOGY OF PHARMACEUTICAL INTERMEDIATES METHYLAMINE HYDROCHLORIDE

以1,8-二氮杂二环十一碳-7-烯为催化剂,硫酸二甲酯(Me2SO4)作为甲基化试剂,制备了甲氧胺盐酸盐。分析了反应机理,考察了溶剂、反应温度、反应时间、pH值及摩尔配比等因素对实验结果的影响。结果表明,较佳合成工艺为:以二氯甲烷和甲醇(体积比2∶1)混合物为溶剂,反应物摩尔比1∶0.7,pH值9~10,反应温度10℃,反应时间6h,总收率达到86.2%。

The methylation reaction of Hydroxylamine was studied by using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as catalyst and dimethyl sulfate (Me 2SO 4) as methylation reagent.The reaction mechanism was analyzed, and the effects of solvent, reaction temperature, reaction time, pH value and molar ratio on the experimental results were investigated. The result showed that the optimumreactions were as follows: a mixture of two chloromethane and methanol (volume ratio 2∶1) as a solvent, hydroxylamine hydrochloride and dimethyl sulfate methylation, with molar ratio of 1∶ 0.7, pH value of 9-10, reaction temperature 10 ℃, reaction time 6 h, the total yield reached 86.2%.This process can use the second methyl of some dimethyl sulfate to reduce the amount of dimethyl sulfate, and provide a technical reference for the industrial production of methylamine hydrochloride.