以2-香豆冉酮为原料、甲酸甲酯/NaH为甲酰化试剂、对甲苯磺酸甲酯为甲基化试剂，通过"一锅"反应得到3-甲氧甲烯基-2-香豆冉酮，进一步以N-羟基丁二酰亚胺（NHSI）为催化剂，3-甲氧甲烯基-2-香豆冉酮在甲醇中与4，6-二氯嘧啶反应得到嘧菌酯中间体2-[2-（6-氯嘧啶-4-基氧基）苯基]-3，3-二甲氧基丙酸甲酯。考察了碱、催化剂用量、反应温度等对产率的影响，优选的最佳反应条件为：反应温度为60℃、反应时间为6 h、n（甲氧甲烯基香豆冉酮）：n（二氯嘧啶）：n（碳酸钾）：n（NHSI）=1：1：1.2：0.2，此时产率为84.5%。相比传统方法，该方法无需低温、无需使用甲醇钠、反应时间较短。初步放大实验中，反应扩大10倍后仍具有较高的产率。

3-Methoxymethyl-2-coumarinone is obtained through a one-pot version by using 2-coumarinone as feedstock, methyl formate/NaH as formylating agent, and methyl p-toluene sulfonate as methylating agent.Then, a reaction between 3-methoxymethyl-2-coumarinone and 4, 6-dichloroquine in methanol is catalyzed over N-hydroxybutyl succinimide (NHSI) to prepare methyl 2-(2-((6-chloropyrimidin-4-yl)oxy)phenyl)-3, 3-dimethoxypropanoate that is the key intermediate of azoxystrobin.The influences of alkali dosage, catalyst dosage and reaction temperature on the yield are investigated.The optimal reaction conditions are obtained below:the reaction has been carried out at 60℃ for 6 h with n(3-methoxymethyl-2-coumarinone):n(4, 6-dichloroquine):n(K₂CO₃):n(NHSI)=1:1:1.2:0.2.Under the optimal conditions, the yield is 84.5%.Comparing with traditional method, this method has the advantages such as the needless of low temperature and sodium methoxide, and a shorter reaction time.A preliminary scale-up experiment is conducted for this method, and the yield is still high after the reaction scale is expanded by 10 times.

蒋达洪(1976-),男,博士,副教授,主要从事有机合成研究,jiangdh@gdupt.edu.cn。